Antimicrobial agents

ABSTRACT

The invention provides a compound of formula I: or a salt thereof, wherein R 3 -R 8  and X and Y have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as antibacterial agents.

PRIORITY OF INVENTION

This application claims priority to U.S. Provisional Application Nos.61/358,759, filed 25 Jun. 2010; 61/376,993, filed 25 Aug. 2010;61/428,791, filed 30 Dec. 2010; and 61/430,058, filed 5 Jan. 2011.

BACKGROUND OF THE INVENTION

The emergence of Multidrug Resistant (MDR) bacterial pathogens (e.g.methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacterbaumannii-calcoaceticus complex (ABC), etc.) has increased concerns asto the adequacy of current antimicrobials and pathogen treatmentmethods. The lethality of such pathogens, particularly MRSA, has oftenled to treatment methods that are experimental or would otherwisenormally be avoided in standard clinical practice. For example, theantibiotic colistin was traditionally considered too nephrotoxic andneurotoxic for clinical use, but is nevertheless used to treat many MDRbacterial infections due to a paucity of available active drugs. Thegrowing threat from MDR pathogens highlights a critical need foradditional antimicrobials. In this connection, there is a pressing needfor new antibiotics that exhibit novel mechanisms of action or that areable to circumvent known resistance pathways.

Elements of the bacterial cell division machinery present appealingtargets for antimicrobial compounds because (i) they are essential forbacterial viability, (ii) they are widely conserved among bacterialpathogens, and (iii) they often have markedly different structures thantheir eukaryotic homologs. One such protein that has been identified asa potential target is the FtsZ protein. During the division process,FtsZ, along with approximately 15 other proteins, assemble at mid-cellinto a large cell division complex (termed the divisome), ultimatelyfacilitating cell cytokinesis. More importantly, FtsZ is widelyconserved among many bacterial strains.

SUMMARY OF THE INVENTION

In one embodiment the invention provides compounds that displayantimicrobial activity. Accordingly, the invention provides a compoundof formula I:

wherein R³-R⁸, X, and Y have the values defined in a), b), or c) below:a) X is N; Y is C(R²); and R³ is R^(e); or

X is N; Y is C(R¹⁵); and R³ is R^(c); or

X is C(R¹); Y is N; and R³ is R^(c) or

X is C(R¹⁶); Y is C(R¹¹); and R³ is R^(e); or

X is C(R¹); Y is C(R¹²); and R³ is R^(e); or

X is C(R³⁰); Y is C(R³¹); and R³ is R^(e); or

X is N⁺—R¹³ (Z⁻); Y is C(R¹²); and R³ is R^(c); or

X is N; Y is C(R¹²); and R³ is R^(e) or

X is C(R¹⁰) or C(R³¹); Y is N⁺—R¹⁴(Z⁻); and R³ is R^(c); or

X is C(R¹⁰) or C(R³¹); Y is N; and R³ is R^(c);

R¹ is R^(y) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

R² is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

at least one of R⁴, R⁵, R⁶, R⁷, R⁸, and R³¹ is aryl or heteroarylwherein each aryl or heteroaryl is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(d); and the remainder of R⁴, R⁵, R⁶, R⁷,and R⁸ are each independently H, halo, cyano, nitro, hydroxy, carboxy,trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p),—S(O)₂R^(p), —S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); whereinany alkyl is optionally substituted with one or more (e.g. 1, 2, 3, or4) R^(a); and any remaining R³¹ is —C(═NR^(hb))—NR^(hc)R^(hd),—NR^(he)—C(═NR^(hb))—NR^(hc)R^(hd), —NR^(ke)—C(═NR^(kb))R^(ke), or(C₁-C₆)alkyl which is substituted with one or more groups selected from—C(═NR^(hb))—NR^(hc)R^(hd), —NR^(he)—C(═NR^(hb))—NR^(hc)R^(hd), and—NR^(ke)—C(═NR^(kb))R^(ke); wherein any aryl, or heteroaryl of R⁴, R⁵,R⁶, R⁷, R⁸, and R³¹ is optionally substituted with one or more (e.g. 1,2, 3, or 4) R^(b);

each R¹⁰ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl of R¹⁰ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryloxy, or heteroaryloxy ofR¹⁰ is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹¹ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R¹² is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹² is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R¹² is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹³ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

each R¹⁴ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

R¹⁵ is R^(x) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

R¹⁶ is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

each R³⁰ is H or (C₁-C₆)alkyl,

each R^(a) is independently selected from halo, cyano, nitro, hydroxy,carboxy, oxo, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h);

each R^(b) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy,(C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h);

each R^(c) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl other than phenyl,heteroaryl other than pyrid-4-yl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(c) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R^(c) is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R^(d) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein each aryl, heteroaryl, aryloxy, and heteroaryloxyis optionally substituted with one or more (e.g. 1, 2, 3, or 4) groupsindependently selected from halo, cyano, nitro, hydroxy, carboxy,trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, and—NR^(g)R^(h);

each R^(e) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R^(e) is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(e) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R^(g) and R^(h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(g) and R^(h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(g)and R^(h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(m) and R^(n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(m) and R^(n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆) alkyl of R^(m)and R^(n) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(p) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl;

each R^(q) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(s) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(t) and R^(u) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(t) and R^(u)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(x) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(y) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(z) is independently —C(═NR^(j))—NR^(m)R^(n), or—NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(hb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(hc) and R^(hd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(hc) and R^(hd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(hc)and R^(hd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(hm)R^(hn);

each R^(he) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(hm) and R^(hn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(hm) and R^(hn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(kb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(ke) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

the bond represented by ---- is present; and

each Z⁻ is independently an acceptable counterion;

b) wherein:

X is W—R⁵¹;

Y is C(R⁵²);

W is N; R⁵¹ is absent; or

W is N⁺D⁻; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; or

W is C; R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), or(C₁-C₆)alkyl that is substituted with one or more R^(5f);

R⁵² is a ring selected from phenyl, pyridyl, and[D⁻N⁺—(C₁-C₆)alkylpyridyl], which ring is optionally substituted withone or more groups selected from methylenedioxy, Z—R^(5x), R^(5f),R^(5da), and (C₁-C₆)alkyl that is substituted with one or more R^(5f);and which ring is also optionally substituted with a group R^(6′), at aposition ortho to the position where R⁵² connects with the remainder offormula I;

R⁶ and R⁷ taken together can be methylenedioxy or each R⁶ and R⁷ isindependently selected from H, Z—R^(5x), R^(5f), and (C₁-C₆)alkyl thatis substituted with one or more R^(5f);

R⁸ is hydrogen, (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl wherein each(C₁-C₆)alkyl of R⁸ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, and —NR^(5g)R^(5h), andwherein each aryl of R⁸ is optionally substituted with one or moregroups independently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano,nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,R^(5s), and —NR^(5g)R^(5h);

each Z is independently selected from —O—, —S—, and —N(R^(5y))—;

at least one of R³, R⁴, R⁵, and R^(6′) is selected from hydroxy,carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; and the remainder of R³, R⁴, R⁵, and R^(6′)are independently selected from H, hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, and (C₁-C₆)alkanoyl ofR³, R⁴, R⁵, and R^(6′) is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, —S(O)₂NR^(5g)R^(5h),—N(R^(5j))S(O)₂R^(5k), —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h); and wherein eacharyl and heteroaryl of R³, R⁴, R⁵, and R^(6′) is optionally substitutedwith one or more groups independently selected from (C₁-C₆)alkyl, halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy,aryloxy, nitro, sulfo, —S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k),R^(5s), —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), and (C₁-C₆)alkylsubstituted with one or more groups independently selected from—N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h);

each R^(5a) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5b) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5c) and R^(5d) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5c) and R^(5d)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5c)and R^(5d) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5e) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5f) is independently selected from —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), and—NR^(5g)R^(5h);

each R^(5g) and R^(5h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5g) and R^(5h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5g)and R^(5h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5k) is independently selected from (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5m) and R^(5n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5m) and R^(5n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5s) is independently trifluoromethyl, trifluoromethoxy, aryl, orheteroaryl, wherein each aryl and heteroaryl is optionally substitutedwith one or more (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), trifluoromethyl,trifluoromethoxy, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h);

each R^(5u) and R^(5v) is independently selected from H and(C₁-C₆)alkyl;

each R^(5x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(5u)R^(5v);

each R^(5y) is independently selected from H and (C₁-C₆)alkyl;

each D⁻ is independently a counter anion;

each R^(5cb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5cc) and R^(5cd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5cc) and R^(5cd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5cc)and R^(5cd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5cm)R^(5cn);

each R^(5ce) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5cm) and R^(5cn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5cm) and R^(5cn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5da) is carboxy or (C₁-C₆)alkoxycarbonyl; and

the bond represented by ---- is present;

c) wherein:

X is ⁺N(R⁸¹)(R⁸²)B⁻;

Y is C(R⁸³);

R³ is:

A is N or C—R^(4′);

any adjacent R⁶, R⁷, R⁸, R^(4′) and R^(5′) taken together can optionallybe methylenedioxy and each remaining R⁶, R⁷, R⁸, R^(4′) and R^(5′) isindependently selected from H, fluoro, R^(8bb), and Z—R^(8x);

each Z is independently selected from —O—, —S—, and —N(R^(8y))—;

at least one of R⁴, R⁵, R^(2′), R^(3′), and R^(6′) is selected fromhydroxy, carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl,heteroaryl, heteroaryl(C₁-C₆)alkyl, arylalkanoyl, andheteroarylalkanoyl; and the remainder of R⁴, R⁵, R^(2′), R^(3′), andR^(6′) are independently selected from hydrogen, halo, hydroxy, carboxy,cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; or R^(6′) and R⁸¹ taken together are —(CR¹³₂)₂— or —CR¹⁴═CR¹⁴—; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and (C₁-C₆)alkanoyl of R⁴,R⁵, R^(2′), R^(3′), and R^(6′) is optionally substituted with one ormore groups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); andwherein each aryl, and heteroaryl of R⁴, R⁵, R^(2′), R^(3′), and R^(6′)is optionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

the bond represented by ---- is present and R⁸² is absent except asdefined below when R⁸¹ and R^(8a) taken together with the atoms to whichthey are attached form a 5- or 6-membered heterocyclic ring or a 5- or6-membered heteroaryl ring;

R⁸¹ is absent and B⁻ is absent; or R⁸¹ is H or (C₁-C₆)alkyl and B⁻ iscounterion;

or R⁸¹ and R^(8a) taken together with the atoms to which they areattached form a 5- or 6-membered heterocyclic ring or a 5- or 6-memberedheteroaryl ring, wherein a) when the bond represented by ---- is presentin the 5- or 6-membered heterocyclic ring or the 5- or 6-memberedheteroaryl ring, R⁸² is absent and B⁻ is a counterion, b) when the bondrepresented by ---- is absent in the 5- or 6-membered heterocyclic ringor the 5- or 6-membered heteroaryl ring, R⁸² is (C₁-C₆)alkyl and B⁻ is acounterion, or c) when the bond represented by ---- is absent in the 5-or 6-membered heterocyclic ring or the 5- or 6-membered heteroaryl ring,R⁸² is absent and B⁻ is absent;

R⁸³ is H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio, aryloxy,arylthio, —NR^(8a)R^(8b), R^(8cc), or cyano; or R^(6′) and R⁸³ takentogether are —(CR¹³ ₂)₂— or —CR¹⁴═CR¹⁴—;

each R¹³ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹³ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹³ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

each R¹⁴ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹⁴ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹⁴ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

R^(8a) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl, orheteroaryl(C₁-C₆)alkyl; wherein each (C₁-C₆)alkyl of R^(8a) isoptionally substituted with one or more groups selected from halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy,—NR^(8g)R^(8h), and aryloxy, and wherein each aryl and heteroaryl ofR^(8a) is optionally substituted with one or more groups selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, —NR^(8g)R^(8h), and aryloxy;

R^(8b) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl,heteroaryl(C₁-C₆)alkyl, —C(═O)—R^(8m), —C(═O)—OR^(8n), —C(═O)—SR^(8p),—C(═O)—NR^(8q)R^(8r), —C(═S)—R^(8m), —C(═S)—OR^(8n), —C(═S)—SR^(8p),—C(═S)—NR^(8q)R^(8r), or —C(═NR^(8c))—R^(8d); wherein each (C₁-C₆)alkylof R^(8b) is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, oxo, carboxy, and aryloxy; and wherein each aryl, andheteroaryl of R^(8b) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, and aryloxy; or R^(8a) and R^(8b)taken together with the nitrogen to which they are attached formaziridino, azetidino, morpholino, piperazino, pyrrolidino, pyrrole,indole, or piperidino, which aziridino, azetidino, morpholino,piperazino, pyrrolidino pyrrole, indole, or piperidino can optionally besubstituted with one or more (C₁-C₆)alkyl;

R^(8c) is hydrogen, (C₁-C₆)alkyl, aryl, or heteroaryl;

R^(8d) is hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio,(C₁-C₆)alkanoyl, or —NR^(8e)R^(8f);

R^(8e) and R^(8f) are each independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(8e) and R^(8f) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8g) and R^(8h) is independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(g) and R^(h) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8j) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8k) is independently selected from (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8m) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8n) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8p) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8q) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl; and each R^(8r) is independently selected fromH, (C₁-C₆)alkyl, cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆)alkyl and heteroaryl(C₁-C₆)alkyl; or R^(8q) and R^(8r)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(8u) and R^(8v) is independently selected from H and(C₁-C₆)alkyl;

each R^(8x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(u)R^(v);

each R^(8y) is independently selected from H and (C₁-C₆)alkyl;

each R^(8aa) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8bb) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

R^(8cc) is (C₁-C₆)alkyl which is substituted with one or more—N⁺(R^(8ha))₃B⁻, —C(═NR^(8hb))—NR^(8hc)R^(8hd),—NR^(8he)—C(═NR^(8hb))—NR^(8hc)R^(8hd), —NR^(8ke)—C(═NR^(8kb))R^(8ke),or —NR^(8ke)—C(═O)—NR^(8kc)R^(8kd);

each R^(8ha) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hc) and R^(8hd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8hc) and R^(8hd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(hc)and R^(hd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(hm)R^(hn);

each R^(8he) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hm) and R^(8hn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8hm) and R^(8hn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(8kb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8kc) and R^(kd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8kc) and R^(8kd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(8kc)and R^(8kd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(8km)R^(8kn);

each R^(8ke) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl; and

each R^(8km) and R^(8kn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8km) and R^(8kn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; and

each B⁻ is a counterion;

or a salt or prodrug thereof.

The invention also provides a composition comprising a compound offormula I, or a pharmaceutically acceptable salt or prodrug thereof, anda pharmaceutically acceptable vehicle.

The invention also provides a method for treating a bacterial infectionin a mammal comprising administering to the mammal an effective amountof a compound of formula I, or a pharmaceutically acceptable salt orprodrug thereof.

The invention also provides a compound of formula I, or apharmaceutically acceptable salt or prodrug thereof for the prophylacticor therapeutic treatment of a bacterial infection.

The invention also provides a compound of formula I, or apharmaceutically acceptable salt or prodrug thereof for use in medicaltreatment.

The invention also provides the use of a compound of formula I, or apharmaceutically acceptable salt or prodrug thereof for the preparationof a medicament for treating a bacterial infection in a mammal.

The invention also provides processes and intermediates disclosed hereinthat are useful for preparing compounds of formula I or salts orprodrugs thereof.

DETAILED DESCRIPTION

The following definitions are used, unless otherwise described: halo isfluoro, chloro, bromo, or iodo. Alkyl, alkenyl, alkynyl and alkoxy, etc.denote both straight and branched groups but reference to an individualradical such as propyl embraces only the straight chain radical (abranched chain isomer such as isopropyl being specifically referred to).In one embodiment alkyl is a (C₁-C₆)alkyl, alkenyl is a (C₂-C₆)alkenyl,alkynyl is a (C₂-C₆)alkynyl and alkoxy is a (C₁-C₆)alkoxy. Aryl denotesa phenyl radical or an ortho-fused bicyclic carbocyclic radical havingabout nine to ten ring atoms in which at least one ring is aromatic.Heteroaryl encompasses a radical of a monocyclic aromatic ringcontaining five or six ring atoms consisting of carbon and one to fourheteroatoms each selected from the group consisting of non-peroxideoxygen, sulfur, and N(Q) wherein Q is absent or is H, O, (C₁-C₄)alkyl,phenyl or benzyl; as well as a radical of an ortho-fused bicyclicheterocycle of about eight to ten ring atoms comprising one to fourheteroatoms each selected from the group consisting of non-peroxideoxygen, sulfur, and N(Q).

As used herein “cycloalkyl” refers to a saturated or partiallyunsaturated cyclic hydrocarbon ring system. In one embodiment“cycloalkyl” includes (C₃-C₆)cycloalkyl which can be cyclopropyl,cyclobutyl, cyclopentyl, or cyclohexyl.

It will be appreciated by those skilled in the art that compounds of theinvention having a chiral center may exist in and be isolated inoptically active and racemic forms. Some compounds may exhibitpolymorphism. It is to be understood that the present inventionencompasses any racemic, optically-active, stereoisomeric, orpolymorphic form, or mixtures thereof, of a compound of the invention,which possess the useful properties described herein, it being wellknown in the art how to prepare optically active forms (for example, byresolution of the racemic form by recrystallization techniques, bysynthesis from optically-active starting materials, by chiral synthesis,or by chromatographic separation using a chiral stationary phase).

It will also be appreciated by those skilled in the art that certaincompounds of the invention can exist in more than one tautomeric form.For example, a substituent of formula —NH—C(═NH)—NH₂ in a compound offormula (I) could exist in tautomeric form as —N═C(NH₂)—NH₂, or asubstituent of formula —NH—C(═NH)—CH₃ in a compound of formula (I) couldexist in tautomeric form as —N═C(NH₂)—CH₃. The present inventionencompasses all tautomeric forms of a compound of formula I as well asmixtures thereof that can exist in equilibrium with non-charged entitiesdepending upon pH, which possess the useful properties described herein.

Specific values listed below for radicals, substituents, and ranges, arefor illustration only; they do not exclude other defined values or othervalues within defined ranges for the radicals and substituents.

Specifically, (C₁-C₆)alkyl can be methyl, ethyl, propyl, isopropyl,butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl, or hexyl;(C₃-C₆)cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, orcyclohexyl; (C₁-C₆)alkoxy can be methoxy, ethoxy, propoxy, isopropoxy,butoxy, iso-butoxy, sec-butoxy, pentoxy, 3-pentoxy, or hexyloxy;(C₁-C₆)alkanoyl can be formyl, acetyl, propanoyl, butanoyl, pentanoyl,or hexanoyl; (C₁-C₆)alkoxycarbonyl can be methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl,pentoxycarbonyl, or hexyloxycarbonyl; aryl can be phenyl, indenyl, ornaphthoyl; and heteroaryl can be furyl, imidazolyl, triazolyl,triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazoyl, pyrazolyl,pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, (or its N-oxide), thienyl,pyrimidinyl (or its N-oxide), indolyl, benzimidazole, isoquinolyl (orits N-oxide) or quinolyl (or its N-oxide).

As used herein the term “aryl(C₁-C₆)alkyl” refers to a (C₁-C₆)alkylradical in which one or more of the hydrogen atoms of the (C₁-C₆)alkylradical is replaced with an aryl radical. As used herein the term“heteroaryl(C₁-C₆) alkyl” refers to a (C₁-C₆)alkyl radical in which oneor more of the hydrogen atoms of the (C₁-C₆)alkyl radical is replacedwith a heteroaryl radical.

As used herein, “an aryl(C₁-C₆)alkanoyl group” refers to a group of theformula aryl-(C₁-C₆)alkanoyl-, where aryl and (C₁-C₆)alkanoyl aredefined herein. Such aryl(C₁-C₆)alkanoyl groups may include, but are notlimited to, benzoyl, 4-phenylbenzoyl, and naphthoyl, and the like. Asused herein, “a heteroaryl(C₁-C₆)alkanoyl group” refers to a group ofthe formula heteroaryl-(C₁-C₆)alkanoyl-, where heteroaryl and(C₁-C₆)alkanoyl are defined herein.

As used herein, “an aryloxy group” refers to a group of the formulaaryl-O—, where aryl is as defined herein. Such aryloxy groups mayinclude, but are not limited to, phenoxy, 4-phenylphenoxy, andnaphthyloxy, and the like. As used herein, “an arylthio group” refers toa group of the formula aryl-S—, where aryl is as defined herein. Sucharylthio groups may include, but are not limited to, phenylthio,4-phenylphenylthio, and naphthylthio, and the like. As used herein, “aheteroaryloxy group” refers to a group of the formula heteroaryl-O—,where hetereoaryl is as defined herein.

A specific compound of the invention is a compound of formula (I)wherein R³-R⁸, X, and Y have the values defined in a), b), and c) below:

a) X is N; Y is C(R²); and R³ is R^(e); or

X is N; Y is C(R¹⁵); and R³ is R^(c); or

X is C(R¹); Y is N; and R³ is R^(c) or

X is C(R¹⁶); Y is C(R¹¹); and R³ is R^(e); or

X is C(R¹); Y is C(R¹²); and R³ is R^(e); or

X is C(R³⁰); Y is C(R³¹); and R³ is R^(e); or

X is N⁺—R¹³(Z⁻); Y is C(R¹²); and R³ is R^(c); or

X is C(R¹⁰); Y is N⁺—R¹⁴(Z⁻); and R³ is R^(c);

R¹ is R^(y) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

R² is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

at least one of R⁴, R⁵R⁶ and R⁷ is aryl or heteroaryl wherein each arylor heteroaryl is optionally substituted with one or more (e.g. 1, 2, 3,or 4) R^(d); and the remainder of R⁴R⁵R⁶ and R⁷ are each independentlyH, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R⁴, R⁵, R⁶ and R⁷ is optionally substitutedwith one or more (e.g. 1, 2, 3, or 4) R^(b);

R⁸ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein any alkyl of R⁸ isoptionally substituted with one or more (e.g. 1, 2, 3, or 4) R^(a); andwherein any aryl, or heteroaryl of R⁸ is optionally substituted with oneor more (e.g. 1, 2, 3, or 4) R^(b);

each R¹⁰ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl of R¹⁰ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryloxy, or heteroaryloxy ofR¹⁰ is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹¹ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R¹² is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹² is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R¹² is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹³ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

each R¹⁴ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

R¹⁵ is R^(x) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

R¹⁶ is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

each R³⁰ is H or (C₁-C₆)alkyl,

each R³¹ is —C(═NR^(hb))—NR^(hc)R^(hd),—NR^(he)—C(═NR^(hb))—NR^(hc)R^(hd), —NR^(ke)—C(═NR^(kb))R^(ke), or(C₁-C₆)alkyl which is substituted with one or more groups selected from—C(═NR^(hb))—NR^(hc)R^(hd), —NR^(he)—C(═NR^(hb))—NR^(hc)R^(hd), and—NR^(ke)—C(═NR^(kb))R^(ke);

each R^(a) is independently selected from halo, cyano, nitro, hydroxy,carboxy, oxo, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h);

each R^(b) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy,(C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h);

each R^(c) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl other than phenyl,heteroaryl other than pyrid-4-yl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(c) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R^(c) is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R^(d) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein each aryl, heteroaryl, aryloxy, and heteroaryloxyis optionally substituted with one or more (e.g. 1, 2, 3, or 4) groupsindependently selected from halo, cyano, nitro, hydroxy, carboxy,trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, and—NR^(g)R^(h);

each R^(e) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R^(e) is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(e) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R^(g) and R^(h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(g) and R^(h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(g)and R^(h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(m) and R^(n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(m) and R^(n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆) alkyl of R^(m)and R^(n) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(p) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl;

each R^(q) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(s) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(t) and R^(u) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(t) and R^(u)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(x) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(y) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(z) is independently —C(═NR^(j))—NR^(m)R^(n), or—NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(hb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(hc) and R^(hd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(hc) and R^(hd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(hc)and R^(hd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(hm)R^(hn);

each R^(he) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(hm) and R^(hn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(hm) and R^(hn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(kb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(ke) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

the bond represented by ---- is present; and

each Z⁻ is independently an acceptable counterion;

b) wherein:

X is W—R⁵¹;

Y is C(R⁵²);

W is N; R⁵¹ is absent; or

W is N⁺D⁻; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; or

W is C; R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5c)—C(═NR^(5b))—NR^(c)R^(d), —NR^(5g)R^(5h),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), or(C₁-C₆)alkyl that is substituted with one or more R^(5f);

R⁵² is a ring selected from phenyl, pyridyl, and[D⁻N⁺—(C₁-C₆)alkylpyridyl], which ring is optionally substituted withone or more groups selected from methylenedioxy, Z—R^(5x), R^(5f),R^(5da), and (C₁-C₆)alkyl that is substituted with one or more R^(5f);and which ring is also optionally substituted with a group R^(6′), at aposition ortho to the position where R⁵² connects with the remainder offormula I;

R⁶ and R⁷ taken together can be methylenedioxy or each R⁶ and R⁷ isindependently selected from H, Z—R^(5x), R^(5f), and (C₁-C₆)alkyl thatis substituted with one or more R^(5f);

R⁸ is hydrogen, (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl wherein each(C₁-C₆)alkyl of R⁸ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, and —NR^(5g)R^(5h), andwherein each aryl of R⁸ is optionally substituted with one or moregroups independently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano,nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,R^(5s), and —NR^(5g)R^(5h);

each Z is independently selected from —O—, —S—, and —N(R^(5y))—;

at least one of R³, R⁴, R⁵, and R^(6′) is selected from hydroxy,carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; and the remainder of R³, R⁴, R⁵, and R^(6′)are independently selected from H, hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, and (C₁-C₆)alkanoyl ofR³, R⁴, R⁵, and R^(6′) is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, —S(O)₂NR^(5g)R^(5h),—N(R^(5j))S(O)₂R^(5k), —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h); and wherein eacharyl and heteroaryl of R³, R⁴, R⁵, and R^(6′) is optionally substitutedwith one or more groups independently selected from (C₁-C₆)alkyl, halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy,aryloxy, nitro, sulfo, —S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k),R^(5s), —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), and (C₁-C₆)alkylsubstituted with one or more groups independently selected from—N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h);

each R^(5a) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5b) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5c) and R^(5d) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5c) and R^(5d)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5c)and R^(5d) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5e) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5f) is independently selected from —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), and—NR^(g)R^(h);

each R^(5g) and R^(5h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5g) and R^(5h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5g)and R^(5h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5k) is independently selected from (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5m) and R^(5n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5m) and R^(5n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5s) is independently trifluoromethyl, trifluoromethoxy, aryl, orheteroaryl, wherein each aryl and heteroaryl is optionally substitutedwith one or more (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(5g)R^(5h)—N(R^(5j))S(O)₂R^(5k), trifluoromethyl,trifluoromethoxy, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(c)R^(d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h);

each R^(5u) and R^(5v) is independently selected from H and(C₁-C₆)alkyl;

each R^(5x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(5u)R^(5v);

each R^(5y) is independently selected from H and (C₁-C₆)alkyl;

each D⁻ is independently a counter anion;

each R^(5cb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5cc) and R^(5cd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5cc) and R^(5cd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5cc)and R^(5cd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5cm)R^(5cn);

each R^(5ce) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5cm) and R^(5cn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5cm) and R^(5cn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5da) is carboxy or (C₁-C₆)alkoxycarbonyl;

the bond represented by ---- is present;

c) wherein:

X is ⁺N(R⁸¹)(R⁸²)B⁻;

Y is C(R⁸³);

R³ is:

A is N or C—R^(4′);

any adjacent R⁶, R⁷, R⁸, R^(4′) and R^(5′) taken together can optionallybe methylenedioxy and each remaining R⁶, R⁷, R⁸, R^(4′) and R^(5′) isindependently selected from H, fluoro, R^(8bb), and Z—R^(8x);

each Z is independently selected from —O—, —S—, and —N(R^(8y))—;

at least one of R⁴, R⁵, R^(2′), R^(3′), and R^(6′) is selected fromhydroxy, carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl,heteroaryl, heteroaryl(C₁-C₆)alkyl, arylalkanoyl, andheteroarylalkanoyl; and the remainder of R⁴, R⁵, R^(2′), R^(3′), andR^(6′) are independently selected from hydrogen, halo, hydroxy, carboxy,cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; or R^(6′) and R⁸¹ taken together are —(CR¹³₂)₂— or —CR¹⁴═CR¹⁴—; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and (C₁-C₆)alkanoyl of R⁴,R⁵, R^(2′), R^(3′), and R^(6′) is optionally substituted with one ormore groups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); andwherein each aryl, and heteroaryl of R⁴, R⁵, R^(2′), R^(3′), and R^(6′)is optionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

the bond represented by ---- is present and R⁸² is absent except asdefined below when R⁸¹ and R^(8a) taken together with the atoms to whichthey are attached form a 5- or 6-membered heterocyclic ring or a 5- or6-membered heteroaryl ring;

R⁸¹ is absent and B⁻ is absent; or R⁸¹ is H or (C₁-C₆)alkyl and B⁻ iscounterion;

or R⁸¹ and R^(8a) taken together with the atoms to which they areattached form a 5- or 6-membered heterocyclic ring or a 5- or 6-memberedheteroaryl ring, wherein a) when the bond represented by ---- is presentin the 5- or 6-membered heterocyclic ring or the 5- or 6-memberedheteroaryl ring, R⁸² is absent and B⁻ is a counterion, b) when the bondrepresented by ---- is absent in the 5- or 6-membered heterocyclic ringor the 5- or 6-membered heteroaryl ring, R⁸² is (C₁-C₆)alkyl and B⁻ is acounterion, or c) when the bond represented by ---- is absent in the 5-or 6-membered heterocyclic ring or the 5- or 6-membered heteroaryl ring,R⁸² is absent and B⁻ is absent;

R⁸³ is H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio, aryloxy,arylthio, —NR^(8a)R^(8b), R^(8cc), or cyano; or R^(6′) and R⁸³ takentogether are —(CR¹³ ₂)₂— or —CR¹⁴═CR¹⁴—;

each R¹³ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹³ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹³ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

each R¹⁴ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹⁴ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹⁴ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

R^(8a) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl, orheteroaryl(C₁-C₆)alkyl; wherein each (C₁-C₆)alkyl of R^(8a) isoptionally substituted with one or more groups selected from halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy,—NR^(8g)R^(8h), and aryloxy, and wherein each aryl and heteroaryl ofR^(8a) is optionally substituted with one or more groups selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, —NR^(8g)R^(8h), and aryloxy;

R^(8b) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl,heteroaryl(C₁-C₆)alkyl, —C(═O)—R^(8m), —C(═O)—OR^(8n), —C(═O)—SR^(8p),—C(═O)—NR^(8q)R^(8r), —C(═S)—R^(8m), —C(═S)—OR^(8n), —C(═S)—SR^(8p),—C(═S)—NR^(8q)R^(8r), or —C(═NR^(8c))—R^(8d); wherein each (C₁-C₆)alkylof R^(8b) is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, oxo, carboxy, and aryloxy; and wherein each aryl, andheteroaryl of R^(8b) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, and aryloxy; or R^(8a) and R^(8b)taken together with the nitrogen to which they are attached formaziridino, azetidino, morpholino, piperazino, pyrrolidino, pyrrole,indole, or piperidino, which aziridino, azetidino, morpholino,piperazino, pyrrolidino pyrrole, indole, or piperidino can optionally besubstituted with one or more (C₁-C₆)alkyl;

R^(8c) is hydrogen, (C₁-C₆)alkyl, aryl, or heteroaryl;

R^(8d) is hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio,(C₁-C₆)alkanoyl, or —NR^(8e)R^(8f);

R^(8e) and R^(8f) are each independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(8e) and R^(8f) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8g) and R^(8h) is independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(g) and R^(h) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8j) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8k) is independently selected from (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8m) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8n) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8p) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8q) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl; and each R^(8r) is independently selected fromH, (C₁-C₆)alkyl, cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆)alkyl and heteroaryl(C₁-C₆)alkyl; or R^(8q) and R^(8r)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(8u) and R^(8v) is independently selected from H and(C₁-C₆)alkyl;

each R^(8x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(u)R^(v);

each R^(8y) is independently selected from H and (C₁-C₆)alkyl;

each R^(8aa) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8bb) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h)—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

R^(8cc) is (C₁-C₆)alkyl which is substituted with one or more—N⁺(R^(8ha))₃B⁻, —C(═NR^(8hb))—NR^(8hc)R^(8hd),—NR^(8he)—C(═NR^(8hb))—NR^(8hc)R^(8hd), —NR^(8ke)—C(═NR^(8kb))R^(8ke),or —NR^(8ke)—C(═O)—NR^(8kc)R^(8kd);

each R^(8ha) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hc) and R^(8hd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8hc) and R^(8hd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(hc)and R^(hd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(hm)R^(hn);

each R^(8he) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8hm) and R^(8hn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8hm) and R^(8hn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(8kb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(8kc) and R^(8kd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8kc) and R^(8kd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(8kc)and R^(8kd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(8km)R^(8kn);

each R^(8ke) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl; and

each R^(8km) and R^(8kn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(8km) and R^(8kn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each B⁻ is a counterion; and

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ia) or(Ib):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ic):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Id) or(Ie):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (If) or(Ig):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ih):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ij):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ik):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Im):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (In):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula:

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula:

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula:

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula:

or a salt or prodrug thereof.

A specific value for R⁴ is phenyl, biphenyl, cyclopropyl,tert-butylphenyl, or furyl.

A specific value for R⁵ is phenyl, biphenyl, cyclopropyl,tert-butylphenyl, or furyl.

A specific value for R⁶ is phenyl, biphenyl, cyclopropyl,tert-butylphenyl, or furyl.

A specific value for R⁷ is phenyl, biphenyl, cyclopropyl,tert-butylphenyl, or furyl.

A specific value for R^(x) is —NR^(m)R^(n).

A specific value for R^(x) is —N⁺(R^(s))₃Z⁻.

A specific value for R^(x) is —C(═NR^(j))—NR^(m)R^(n).

A specific value for R^(x) is —NR^(q)—C(═NR^(j))—NR^(m)R^(n).

A specific value for R^(y) is —NR^(m)R^(n).

A specific value for R^(y) is —N⁺(R^(s))₃Z⁻.

A specific value for R^(y) is —C(═NR^(j))—NR^(m)R^(n).

A specific value for R^(y) is —NR^(q)—C(═NR^(j))—NR^(m)R^(n).

A specific value for R^(z) is —C(═NR^(j))—NR^(m)R^(n).

A specific value for R^(z) is —NR^(q)—C(═NR^(j))—NR^(m)R^(n)

A specific compound of the invention is a compound which is:

or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

or a salt or prodrug thereof.

A specific value for Z⁻ is: Cl⁻, Br⁻, I⁻, CH₃SO₃ ⁻, CF₃SO₃ ⁻,p-CH₃C₆H₄SO₃ ⁻, citrate, tartrate, malate, fumarate, formate, oracetate.

A specific compound of the invention is a compound of formula (I):wherein:

R¹ is R^(y) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

R² is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

at least one of R⁴ R⁵ R⁶ and R⁷ is aryl or heteroaryl wherein each arylor heteroaryl is optionally substituted with one or more (e.g. 1, 2, 3,or 4) R^(d); and the remainder of R⁴, R⁵, R⁶ and R⁷ are eachindependently H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R⁴, R⁵, R⁶ and R⁷ is optionally substitutedwith one or more (e.g. 1, 2, 3, or 4) R^(b);

R⁸ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein any alkyl of R⁸ isoptionally substituted with one or more (e.g. 1, 2, 3, or 4) R^(a); andwherein any aryl, or heteroaryl, of R⁸ is optionally substituted withone or more (e.g. 1, 2, 3, or 4) R^(b);

X is N; Y is C(R²); and R³ is R^(e); or

X is N; Y is C(R¹⁵); and R³ is R^(c); or

X is C(R¹); Y is N; and R³ is R^(c) or

X is C(R¹⁶); Y is C(R¹¹); and R³ is R^(e); or

X is C(R¹); Y is C(R¹²); and R³ is R^(e); or

X is N⁺—R¹³(Z⁻); Y is C(R¹²); and R³ is R^(c); or

X is C(R¹⁰); Y is N⁺—R¹⁴(Z⁻); and R³ is R^(c);

each R¹⁰ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl of R¹⁰ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryloxy, or heteroaryloxy ofR¹⁰ is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹¹ is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹¹ is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R¹² is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R¹² is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R¹² is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R¹³ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

each R¹⁴ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl;

R¹⁵ is R^(x) or (C₁-C₆)alkyl that is substituted with one or more R^(x);

R¹⁶ is R^(z) or (C₁-C₆)alkyl that is substituted with one or more R^(y);

each R^(a) is independently selected from halo, cyano, nitro, hydroxy,carboxy, oxo, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h),

each R^(b) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy,(C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p), —S(O)₃R^(p),—S(O)₂NR^(g)R^(h), and —NR^(g)R^(h); wherein each aryl, heteroaryl,aryloxy, and heteroaryloxy is optionally substituted with one or more(e.g. 1, 2, 3, or 4) groups independently selected from halo, cyano,nitro, hydroxy, carboxy, trifluoromethyl, trifluoromethoxy,(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, (C₁-C₆)alkylthio, —S(O)R^(p), —S(O)₂R^(p),—S(O)₃R^(p), —S(O)₂NR^(g)R^(h), and —NR^(g)R^(h);

each R^(c) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl other than phenyl,heteroaryl other than pyrid-4-yl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein any alkyl and any alkyl or alkanoyl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(c) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(a); and wherein any aryl, heteroaryl, orany aryl or heteroaryl portion of any aryl(C₁-C₆)alkyl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoylof R^(c) is optionally substituted with one or more (e.g. 1, 2, 3, or 4)R^(b);

each R^(d) is independently selected from halo, cyano, nitro, hydroxy,carboxy, trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl,(C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and—NR^(g)R^(h); wherein each aryl, heteroaryl, aryloxy, and heteroaryloxyis optionally substituted with one or more (e.g. 1, 2, 3, or 4) groupsindependently selected from halo, cyano, nitro, hydroxy, carboxy,trifluoromethyl, trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, and—NR^(g)R^(h);

each R^(e) is H, halo, cyano, nitro, hydroxy, carboxy, trifluoromethyl,trifluoromethoxy, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(g)R^(h); wherein any alkyl and any alkyl oralkanoyl portion of any aryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl,aryl(C₁-C₆)alkanoyl or heteroaryl(C₁-C₆)alkanoyl of R^(e) is optionallysubstituted with one or more (e.g. 1, 2, 3, or 4) R^(a); and wherein anyaryl, heteroaryl, or any aryl or heteroaryl portion of anyaryl(C₁-C₆)alkyl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl orheteroaryl(C₁-C₆)alkanoyl of R^(e) is optionally substituted with one ormore (e.g. 1, 2, 3, or 4) R^(b);

each R^(g) and R^(h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(g) and R^(h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(g)and R^(h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(m) and R^(n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(m) and R^(n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆) alkyl of R^(m)and R^(n) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(t)R^(u);

each R^(p) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl;

each R^(q) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(s) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(t) and R^(u) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(t) and R^(u)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(x) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(y) is independently —NR^(m)R^(n), —N⁺(R^(s))₃Z⁻,—C(═NR^(j))—NR^(m)R^(n), or —NR^(q)—C(═NR^(j))—NR^(m)R^(n);

each R^(z) is independently —C(═NR^(j))—NR^(m)R^(n), or—NR^(q)—C(═NR^(j))—NR^(m)R^(n);

the bond represented by ---- is present; and

each Z⁻ is independently an acceptable counterion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (I):

wherein:

X is W—R⁵¹;

Y is C(R⁵²);

W is N; R⁵¹ is absent; or

W is N⁺A⁻; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻ iscounter anion; or

W is C; R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)C(═O)—NR^(5cc)R^(5cd), or(C₁-C₆)alkyl that is substituted with one or more R^(5f); and A⁻ isabsent;

R⁵² is a ring selected from:

wherein:

any adjacent R⁶, R⁷, R^(4′) and R^(5′) taken together can optionally bemethylenedioxy and each remaining R⁶, R⁷, R^(4′) and R^(5′) isindependently selected from H, Z—R^(x), R^(f), and (C₁-C₆)alkyl that issubstituted with one or more R^(f);

the bond represented by ---- is present;

R^(7′) is absent and B⁻ is absent; or R^(7′) is (C₁-C₆)alkyl and B⁻ is acounterion; and

R^(8′) is absent and B⁻ is absent; or R^(8′) is (C₁-C₆)alkyl and B⁻ is acounterion.

A specific compound of the invention is a compound of formula Va:

wherein:

X is N or C(R^(56′));

W is N; R⁵¹ is absent; and A⁻ is absent; or

W is N; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻ iscounter anion; or

W is C; R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), or(C₁-C₆)alkyl that is substituted with one or more R^(5f); and A⁻ isabsent;

Y is N; R^(52′) is absent; and B⁻ is absent; or

Y is N; R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and B⁻ iscounter anion; or

Y is C; R^(52′) is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5ce)—C(═NR^(5cb))R^(5ce),—NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), —NR^(5g)R^(5h), or (C₁-C₆)alkyl that issubstituted with one or more R^(5f); and B⁻ is absent;

any adjacent R⁶, R⁷, R^(53′), R^(54′) and R^(55′) taken together canoptionally be methylenedioxy and each remaining R⁶, R⁷, R^(53′), R^(54′)and R^(55′) is independently selected from H, Z—R^(5x), R^(5f), and(C₁-C₆)alkyl that is substituted with one or more R^(5f); or R^(54′) canbe R^(5da);

R⁸ is hydrogen, (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl wherein each(C₁-C₆)alkyl of R⁸ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, and —NR^(5g)R^(5h), andwherein each aryl of R⁸ is optionally substituted with one or moregroups independently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano,nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,R^(5s), and —NR^(5g)R^(5h);

each Z is independently selected from —O—, —S—, and —N(R^(5y))—;

at least one of R³, R⁴, R⁵, and R^(56′) is selected from hydroxy,carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; and the remainder of R³, R⁴, R⁵, and R^(56′)are independently selected from H, hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, and (C₁-C₆)alkanoyl ofR³, R⁴, R⁵, and R^(56′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), or —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and—NR^(5g)R^(5h); and wherein each aryl and heteroaryl of R³, R⁴, R⁵, andR^(56′) is optionally substituted with one or more groups independentlyselected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(5g)R^(5h),—N(R^(5j))S(O)₂R^(5k), Rv^(s), —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), or —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5gv)R^(h), and (C₁-C₆)alkyl substituted with one or more groupsindependently selected from —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),or —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h);

each R^(5a) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5b) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5c) and R^(5d) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5c) and R^(5d)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(c)and R^(5d) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NRv^(m)R^(5n);

each R^(5e) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5f) is independently selected from —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5ce)—C(═NR^(5cb))R^(5ce), —NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), and—NR^(5g)R^(5h);

each R^(5g) and R^(5h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5g) and R^(5h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5g)and R^(5h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5k) is independently selected from (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5m) and R^(5n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5m) and R^(5n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5s) is independently trifluoromethyl, trifluoromethoxy, aryl, orheteroaryl, wherein each aryl and heteroaryl is optionally substitutedwith one or more (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(g)R^(h), —N(R^(j))S(O)₂R^(k), trifluoromethyl,trifluoromethoxy, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h);

each R^(5u) and R^(5v) is independently selected from H and(C₁-C₆)alkyl;

each R^(5x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(5u)R^(5v);

each R^(5y) is independently selected from H and (C₁-C₆)alkyl;

each D⁻ is independently a counter anion;

each R^(5cb) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5cc) and R^(5cd) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5cc) and R^(5cd)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5cc)and R^(5cd) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5cm)R^(5cn);

each R^(5ce) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl; and

each R^(5cm) and R^(5cn) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(cm) and R^(cn)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; and

each R^(5da) is carboxy or (C₁-C₆)alkoxycarbonyl;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (I)wherein:

X is N or C(R^(56′));

W is N; R⁵¹ is absent; and A⁻ is absent; or

W is N; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻ iscounter anion; or

W is C; R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more R^(5f); and A⁻ is absent;

Y is N; R^(52′) is absent; and B⁻ is absent; or

Y is N; R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and B⁻ iscounter anion; or

Y is C; R^(52′) is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═N⁵R^(b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more R^(5f); and B⁻ is absent;

any adjacent R⁶, R⁷, R^(53′), R^(54′) and R^(55′) taken together canoptionally be methylenedioxy and each remaining R⁶, R⁷, R^(53′), R^(54′)and R^(55′) is independently selected from H, Z—R^(5x), R^(5f), and(C₁-C₆)alkyl that is substituted with one or more R^(5f);

R⁸ is hydrogen, (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl wherein each(C₁-C₆)alkyl of R⁸ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, and —NR^(5g)R^(5h), andwherein each aryl of R⁸ is optionally substituted with one or moregroups independently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano,nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,R^(5s), and —NR^(5g)R^(5h);

each Z is independently selected from —O—, —S—, and —N(R^(5y))—;

at least one of R³, R⁴, R⁵, and R^(56′) is selected from hydroxy,carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; and the remainder of R³, R⁴, R⁵, and R^(6′)are independently selected from H, hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, and (C₁-C₆)alkanoyl ofR³, R⁴, R⁵, and R^(56′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), or —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and—NR^(g)R^(h); and wherein each aryl and heteroaryl of R³, R⁴, R⁵, andR^(56′) is optionally substituted with one or more groups independentlyselected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(5g)R^(5h),—N(R^(5j))S(O)₂R^(5k), R^(5s), —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), or NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5g)R^(5h), and (C₁-C₆)alkyl substituted with one or more groupsindependently selected from —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),or —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h);

each R^(5a) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5b) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5c) and R^(5d) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5c) and R^(5d)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(c)and R^(d) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5e) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5f) is independently selected from —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h);

each R^(5g) and ⁵R^(h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5g) and R^(5h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5g)and R^(5h) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n);

each R^(5j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5k) is independently selected from (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5m) and R^(5n) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5m) and R^(5n)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5s) is independently trifluoromethyl, trifluoromethoxy, aryl, orheteroaryl, wherein each aryl and heteroaryl is optionally substitutedwith one or more (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), trifluoromethyl,trifluoromethoxy, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d) and —NR^(5g)R^(5h);

each R^(5u) and R^(5v) is independently selected from H and(C₁-C₆)alkyl;

each R^(5x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(5u)R^(5v);

each R^(5y) is independently selected from H and (C₁-C₆)alkyl; and

each D⁻ is independently a counter anion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (I):

wherein:

X is N or C(R^(56′));

W is N; R⁵¹ is absent; and A⁻ is absent; or

W is N; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻ iscounter anion; or

W is C; R⁵¹ is hydrogen or —NR^(5aa)R^(5bb) and A⁻ is absent; or

W is C; R⁵¹ is —N⁺(R^(5cc))₃; and A⁻ is counter anion;

Y is N; R^(52′) is absent; and B⁻ is absent; or

Y is N; R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and B⁻ iscounter anion; or

Y is C; R^(52′) is hydrogen or —NR^(5dd)R^(5ee); and B⁻ is absent; or

Y is C; R^(52′) is —N⁺(R^(5ff))₃; and B⁻ is counter anion;

any adjacent R⁶, R⁷, R^(53′), R^(54′) and R^(55′) taken together canoptionally be methylenedioxy and each remaining R⁶, R⁷, R^(53′), R^(54′)and R^(55′) is independently selected from H and Z—R^(5x);

R⁸ is hydrogen, (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl wherein each(C₁-C₆)alkyl of R⁸ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo, and —NR^(5g)R^(5h), andwherein each aryl of R⁸ is optionally substituted with one or moregroups independently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano,nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,R^(5s), and —NR^(5g)R^(5h);

each Z is independently selected from —O—, —S—, and —N(R^(5y))—;

at least one of R³, R⁴, R⁵, and R^(56′) is selected from hydroxy,carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, arylalkanoyl, and heteroarylalkanoyl; and theremainder of R³, R⁴, R⁵, and R^(56′) are independently selected from H,hydroxy, carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, aryl(C₁-C₆)alkyl,aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, and (C₁-C₆)alkanoyl ofR³, R⁴, R⁵, and R^(56′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), and —NR^(5g)R^(5h); andwherein each aryl and heteroaryl of R³, R⁴, R⁵, and R^(56′) isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,(C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(5g)R^(5h),—N(R^(5j))S(O)₂R^(5k), R^(5s), and —NR^(5g)R^(5h);

each R^(5g) and R^(5h) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; or R^(5g) and R^(5h)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(5j) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5k) is independently selected from (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl;

each R^(5s) is independently trifluoromethyl, trifluoromethoxy, or aryloptionally substituted with one or more (C₁-C₆)alkyl, halo, hydroxy,cyano, nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro,sulfo, —S(O)₂NR^(5g)R^(5h), —N(R^(5j))S(O)₂R^(5k), trifluoromethyl,trifluoromethoxy, and —NR^(5g)R^(5h);

each R^(5u) and R^(5v) is independently selected from H and(C₁-C₆)alkyl;

each R^(5x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(5u)R^(5v);

each R^(5y) is independently selected from H and (C₁-C₆)alkyl;

each R^(5aa) and R^(5bb) is independently selected from H and(C₁-C₆)alkyl; or R^(5aa) and R^(5bb) together with the nitrogen to whichthey are attached form a aziridino, azetidino, morpholino, piperazino,pyrrolidino or piperidino;

each R^(5cc) is independently selected from H and (C₁-C₆)alkyl

each R^(5dd) and R^(ee) is independently selected from H and(C₁-C₆)alkyl; or R^(5dd) and R^(5ee) together with the nitrogen to whichthey are attached form a aziridino, azetidino, morpholino, piperazino,pyrrolidino or piperidino; and

each R^(5ff) is independently selected from H and (C₁-C₆)alkyl

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vb):

wherein Y is N; R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; andB⁻ is counter anion; or

Y is C; R^(52′) is —N(R^(5ff))₃; and B⁻ is counter anion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vc):

wherein R^(51′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻ iscounter anion;

Y is N; and R^(52′) is absent; or

Y is C; and R^(2′) is hydrogen or —NR^(5dd)R^(5ee);

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vd):

wherein R⁵¹ is hydrogen or —NR^(5aa)R^(5bb);

Y is N; R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and B⁻ iscounter anion; or

Y is C; R^(52′) is —N(R^(5ff))₃; and B⁻ is counter anion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Ve):

wherein R⁵¹ is —N(R^(5cc))₃ and A⁻ is counter anion

Y is N; and R^(52′) is absent; or

Y is C; and R^(52′) is hydrogen or —NR^(5dd)R^(5ee);

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vf):

wherein W is N; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻is counter anion; or

W is C; R⁵¹ is —N(R^(5cc))₃; and A⁻ is counter anion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vg):

wherein W is N; and R⁵¹ is absent; or

W is C; and R⁵¹ is hydrogen or —NR^(5aa)R^(5bb); and

R^(52′) is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and B⁻ is counteranion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vh):

wherein W is N; R⁵¹ is (C₁-C₆)alkyl, aryl, or aryl(C₁-C₆)alkyl; and A⁻is counter anion; or

W is C; R⁵¹ is —N(R^(5cc))₃; and A⁻ is counter anion; and

R^(2′) is hydrogen or —NR^(5dd)R^(5ee);

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vj):

wherein W is N; and R⁵¹ is absent; or

W is C; and R⁵¹ is hydrogen or —NR^(5aa)R^(5bb);

R^(52′) is —N(R^(5ff))₃; and B⁻ is counter anion;

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vj)wherein at least one of R^(53′), R^(54′), and R^(55′) is —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5g)R^(5h), or (C₁-C₆)alkyl that is substituted with one or moregroups independently selected from —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vk):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vk)wherein at least one of R^(53′), R^(54′), and R^(55′) is —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5g)R^(5h), or (C₁-C₆)alkyl that is substituted with one or moregroups independently selected from —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vm):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vm)wherein R^(52′) is hydrogen, —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more groups independently selected from—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vm)wherein R^(52′) is —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more groups independently selected from—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vm)wherein at least one of R^(52′), R^(53′), R^(54′), and R^(55′) is—N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g5)R^(h), or (C₁-C₆)alkyl thatis substituted with one or more groups independently selected from—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vn):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vn)wherein at least one of R⁵¹, R^(53′), R^(54′), and R^(55′) is—N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more groups independently selected from—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h).

A specific compound of the invention is a compound of formula (Vo):

or a salt or prodrug thereof.

A specific compound of the invention is a compound of formula (Vo)wherein at least one of R⁵¹, R^(52′), R^(53′), R^(54′), and R^(55′) is—N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d), or—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5g)R^(5h), or (C₁-C₆)alkyl thatis substituted with one or more groups independently selected from—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and—NR^(5g)R^(5h).

A specific value for R³ is phenyl, benzyl, biphenyl, cyclopropyl, orfuryl.

A specific value for R⁴ is phenyl, biphenyl, cyclopropyl, or furyl.

A specific value for R⁵ is phenyl, biphenyl, cyclopropyl, or furyl.

A specific value for R^(56′) is phenyl, benzyl, biphenyl, cyclopropyl,or furyl.

A specific value for R⁵¹ is methyl.

A specific value for W is C and R⁵¹ is hydrogen.

A specific value for W is C and R⁵¹ is —NR^(g)R^(h).

A specific value for W is C and R⁵¹ is —N⁺(R^(a))₃D⁻.

A specific value for Y is N and R^(52′) is methyl.

A specific value for Y is C and R^(52′) is hydrogen.

A specific value for Y is C and R^(52′)—NR^(g)R^(h).

A specific value for Y is C and R^(52′) is —N⁺(R^(a))₃D⁻.

A specific compound of the invention is a compound wherein at least oneZ is —O—.

A specific compound of the invention is a compound wherein at least oneZ is —S—.

A specific compound of the invention is a compound wherein at least oneZ is —N(R^(5y))—.

A specific compound of the invention is a compound wherein each Z is—O—.

A specific compound of the invention is a compound wherein each Z is—S—.

A specific compound of the invention is a compound wherein Z is—N(R^(5y))—.

A specific value for R^(5x) is (C₁-C₆)alkyl.

A specific compound of the invention is a compound wherein R⁶, R⁷,R^(53′), R^(54′) and R^(55′) are each independently (C₁-C₃)alkoxy.

A specific compound of the invention is a compound wherein R⁶, R⁷,R^(53′), R^(54′) and R^(55′) are each methoxy.

A specific value for R⁶ is (C₁-C₃)alkoxy.

A specific value for R⁶ is methoxy.

A specific value for R⁷ is (C₁-C₃)alkoxy.

A specific value for R⁷ is methoxy.

A specific value for R^(53′) is (C₁-C₃)alkoxy.

A specific value for R^(53′) is methoxy.

A specific value for R^(54′) is (C₁-C₃)alkoxy.

A specific value for R^(54′) is methoxy.

A specific value for R^(55′) is (C₁-C₃)alkoxy.

A specific value for R^(55′) is methoxy.

A specific compound of the invention is a compound wherein R⁶, R⁷,R^(53′), and R^(54′) are each methoxy.

A specific compound of the invention is a compound wherein R⁶, R⁷,R^(54′), and R^(55′) are each methoxy.

A specific compound of the invention is a compound wherein R⁶ and R⁷taken together are methylenedioxy.

A specific compound of the invention is a compound wherein R^(53′) andR^(54′) taken together are methylenedioxy.

A specific compound of the invention is a compound wherein R^(54′) andR^(55′) taken together are methylenedioxy.

A specific compound of the invention is a compound wherein each R^(5s)is independently trifluoromethyl, trifluoromethoxy, or aryl optionallysubstituted with one or more (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(5g)R^(5h), —N(R^(j))S(O)₂R^(5k), trifluoromethyl,trifluoromethoxy, and —NR^(5g)R^(5h);

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(5′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy;or a salt or prodrug thereof.

A specific compound of the invention is a compound which is:

or a salt or prodrug thereof.

A specific compound of the invention is a compound wherein at least oneof least one W, X, Y, R¹, R^(52′), R^(53′), R^(54′), R^(55′), andR^(56′) comprises at least one nitrogen atom.

A specific compound of the invention is a compound of formula (I)wherein:

X is ⁺N(R⁸¹)(R⁸²)B⁻;

Y is C(R⁸³);

A is N or C—R^(4′);

any adjacent R⁶, R⁷, R⁸, R^(4′) and R^(5′) taken together can optionallybe methylenedioxy and each remaining R⁶, R⁷, R⁸, R^(4′) and R^(5′) isindependently selected from H, R^(bb), and Z—R^(x);

each Z is independently selected from —O—, —S—, and —N(R^(y))—;

at least one of R⁴, R⁵, R^(2′), R^(3′), and R^(6′) is selected fromhydroxy, carboxy, cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl,heteroaryl, heteroaryl(C₁-C₆)alkyl, arylalkanoyl, andheteroarylalkanoyl; and the remainder of R⁴, R⁵, R^(2′), R^(3′), andR^(6′) are independently selected from hydrogen, halo, hydroxy, carboxy,cyano, CF₃SO₃—, (C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl,(C₁-C₆)alkoxy, cycloalkyl, aryl(C₁-C₆)alkyl, aryl, heteroaryl,heteroaryl(C₁-C₆)alkyl, aryl(C₁-C₆)alkanoyl, andheteroaryl(C₁-C₆)alkanoyl; or R^(6′) and R¹⁰ taken together are —(CR¹³₂)₂— or —CR¹⁴═CR¹⁴—; wherein each (C₁-C₆)alkyl, (C₂-C₆)alkenyl,(C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and (C₁-C₆)alkanoyl of R⁴,R⁵, R^(2′), R^(3′), and R^(6′) is optionally substituted with one ormore groups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(g)R^(h), —N(R^(j))S(O)₂R^(k), and —NR^(g)R^(h); and whereineach aryl, and heteroaryl of R⁴, R⁵, R^(2′), R^(3′), and R^(6′) isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(aa), —S(O)₂NR^(g)R^(h),—N(R^(j))S(O)₂R^(k), and —NR^(g)R^(h);

the bond represented by ---- is present and R⁸² is absent except asdefined below when R⁸¹ and R^(8a) taken together with the atoms to whichthey are attached form a 5- or 6-membered heterocyclic ring or a 5- or6-membered heteroaryl ring;

R⁸¹ is absent and B⁻ is absent; or R⁸¹ is H or (C₁-C₆)alkyl and B⁻ iscounterion;

or R⁸¹ and R^(8a) taken together with the atoms to which they areattached form a 5- or 6-membered heterocyclic ring or a 5- or 6-memberedheteroaryl ring, wherein a) when the bond represented by ---- is presentin the 5- or 6-membered heterocyclic ring or the 5- or 6-memberedheteroaryl ring, R⁸² is absent and B⁻ is a counterion, b) when the bondrepresented by ---- is absent in the 5- or 6-membered heterocyclic ringor the 5- or 6-membered heteroaryl ring, R⁸² is (C₁-C₆)alkyl and B⁻ is acounterion, or c) when the bond represented by ---- is absent in the 5-or 6-membered heterocyclic ring or the 5- or 6-membered heteroaryl ring,R⁸² is absent and B⁻ is absent;

R⁸³ is H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio, aryloxy,arylthio, —NR^(8a)R^(8b) or cyano; or R^(6′) and R⁸³ taken together are—(CR¹³ ₂)₂— or —CR¹⁴═CR¹⁴—;

each R¹³ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹³ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹³ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

each R¹⁴ is independently H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy or arylthio wherein any (C₁-C₆)alkyl,(C₁-C₆)alkoxy, and (C₁-C₆)alkylthio of R¹⁴ is optionally substitutedwith one or more groups selected from halo, cyano, oxo (═O),(C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy, (C₁-C₆)alkoxy,(C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl, heteroaryl, aryloxy,heteroaryloxy, and —NR^(8e)R^(8f), and wherein any aryloxy, or arylthioof R¹⁴ is optionally substituted with one or more groups selected fromhalo, cyano, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, carboxy, NO₂, hydroxy,(C₁-C₆)alkoxy, (C₁-C₆)alkoxycarbonyl, (C₁-C₆)alkanoyloxy, aryl,heteroaryl, aryloxy, heteroaryloxy, and —NR^(8e)R^(8f);

R^(8a) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl, orheteroaryl(C₁-C₆)alkyl; wherein each (C₁-C₆)alkyl of R^(8a) isoptionally substituted with one or more groups selected from halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy,—NR^(8g)R^(8h), and aryloxy, and wherein each aryl and heteroaryl ofR^(8a) is optionally substituted with one or more groups selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, —NR^(8g)R^(8h), and aryloxy;

R^(8b) is hydrogen, (C₁-C₆)alkyl, aryl, aryl(C₁-C₆)alkyl, heteroaryl,heteroaryl(C₁-C₆)alkyl, —C(═O)—R^(8m), —C(═O)—OR^(8n), —C(═O)—SR^(8p),—C(═O)—NR^(8q)R^(8r), —C(═S)—R^(8m), —C(═S)—OR^(8n), —C(═S)—SR^(8p),—C(═S)—NR^(8q)R^(8r), or —C(═NR^(8c))—R^(8d); wherein each (C₁-C₆)alkylof R^(8b) is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, oxo, carboxy, and aryloxy; and wherein each aryl, andheteroaryl of R^(b) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, and aryloxy; or R^(8a) and R^(8b)taken together with the nitrogen to which they are attached formaziridino, azetidino, morpholino, piperazino, pyrrolidino, pyrrole,indole, or piperidino, which aziridino, azetidino, morpholino,piperazino, pyrrolidino pyrrole, indole, or piperidino can optionally besubstituted with one or more (C₁-C₆)alkyl;

R^(8c) is hydrogen, (C₁-C₆)alkyl, aryl, or heteroaryl;

R^(8d) is hydrogen, (C₁-C₆)alkyl, (C₁-C₆)alkoxy, (C₁-C₆)alkylthio,(C₁-C₆)alkanoyl, or —NR^(e)R^(f);

R^(8e) and R^(8f) are each independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(8e) and R^(8f) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8g) and R^(8h) is independently selected from H, (C₁-C₆)alkyl,cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyland heteroaryl(C₁-C₆)alkyl; or R^(8g) and R^(8h) together with thenitrogen to which they are attached form a aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino;

each R^(8j) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8k) is independently selected from (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each ⁸R^(m) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl;

each R^(8n) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8p) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl, wherein each aryl, and heteroaryl is optionallysubstituted with one or more groups independently selected from(C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl,carboxy, aryloxy, nitro, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

each R^(8q) is independently selected from H, (C₁-C₆)alkyl, cycloalkyl,cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆)alkyl andheteroaryl(C₁-C₆)alkyl; and each R^(8r) is independently selected fromH, (C₁-C₆)alkyl, cycloalkyl, cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆)alkyl and heteroaryl(C₁-C₆)alkyl; or R^(8q) and R^(8r)together with the nitrogen to which they are attached form a aziridino,azetidino, morpholino, piperazino, pyrrolidino or piperidino;

each R^(8u) and R^(8v) is independently selected from H and(C₁-C₆)alkyl;

each R^(8x) is independently selected from (C₁-C₆)alkyl,(C₁-C₆)alkanoyl, and —C(═O)NR^(8u)R^(8v);

each R^(8y) is independently selected from H and (C₁-C₆)alkyl;

each R^(8aa) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h)—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and

each R^(8bb) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h);

or a salt thereof.

A specific value for R⁸³ is H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy, arylthio, —NR^(8a)R^(8b) or cyano.

A specific value for R⁸³ is H, (C₁-C₆)alkyl, (C₁-C₆)alkoxy,(C₁-C₆)alkylthio, aryloxy, or arylthio.

A specific value for R⁸³ is —NR^(8a)R^(8b) or cyano.

A specific value for R^(6′) and R⁸³ taken together are —(CR¹³ ₂)₂— or—CR¹⁴═CR¹⁴—.

A specific compound of the invention is a compound wherein the bondrepresented by ---- is present and R⁸² is absent.

A specific compound of the invention is a compound wherein R⁸¹ andR^(8a) taken together with the atoms to which they are attached form a5- or 6-membered heterocyclic ring or a 5- or 6-membered heteroarylring.

A specific compound of the invention is a compound wherein R⁸¹ is absentand B⁻ is absent.

A specific compound of the invention is a compound wherein R⁸¹ is H or(C₁-C₆)alkyl and B⁻ is a counterion.

A specific compound of the invention is a compound of formula (VIIIa):

wherein R^(6′) is selected from hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl,aryl(C₁-C₆)alkyl, aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl,arylalkanoyl, and heteroarylalkanoyl; wherein each (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and(C₁-C₆)alkanoyl of R^(6′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); andwherein each aryl, and heteroaryl of R^(6′) is optionally substitutedwith one or more groups independently selected from (C₁-C₆)alkyl, halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy,nitro, sulfo, R^(8aa), —S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and—NR^(8g)R^(8h); or a salt thereof.

A specific compound of the invention is a compound of formula (VIIIb):

wherein R^(3′) is selected from hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl,aryl(C₁-C₆)alkyl, aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl,arylalkanoyl, and heteroarylalkanoyl; wherein each (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and(C₁-C₆)alkanoyl of R^(3′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); andwherein each aryl, and heteroaryl of R^(3′) is optionally substitutedwith one or more groups independently selected from (C₁-C₆)alkyl, halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy,nitro, sulfo, R^(8aa), —S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and—NR^(8g)R^(8h); or a salt thereof.

A specific compound of the invention is a compound of formula (VIIIc):

wherein R^(2′) is selected from hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl,aryl(C₁-C₆)alkyl, aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl,arylalkanoyl, and heteroarylalkanoyl; wherein each (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and(C₁-C₆)alkanoyl of R^(2′) is optionally substituted with one or moregroups independently selected from halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, oxo, carboxy, aryloxy, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); andwherein each aryl, and heteroaryl of R^(2′) is optionally substitutedwith one or more groups independently selected from (C₁-C₆)alkyl, halo,hydroxy, cyano, nitro, (C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy,nitro, sulfo, R^(8aa), —S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and—NR^(8g)R^(8h); or a salt thereof.

A specific compound of the invention is a compound of formula (VIIId):

wherein R⁴ is selected from hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl,aryl(C₁-C₆)alkyl, aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl,arylalkanoyl, and heteroarylalkanoyl; wherein each (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and(C₁-C₆)alkanoyl of R⁴ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, oxo, carboxy, aryloxy, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and wherein each aryl, andheteroaryl of R⁴ is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); or asalt thereof.

A specific compound of the invention is a compound of formula (VIIIe):

wherein R⁵ is selected from hydroxy, carboxy, cyano, CF₃SO₃—,(C₁-C₆)alkyl, (C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl,aryl(C₁-C₆)alkyl, aryl, heteroaryl, heteroaryl(C₁-C₆)alkyl,arylalkanoyl, and heteroarylalkanoyl; wherein each (C₁-C₆)alkyl,(C₂-C₆)alkenyl, (C₂-C₆)alkynyl, (C₁-C₆)alkoxy, cycloalkyl, and(C₁-C₆)alkanoyl of R⁵ is optionally substituted with one or more groupsindependently selected from halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, oxo, carboxy, aryloxy, sulfo, —S(O)₂NR^(8g)R^(8h),—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and wherein each aryl, andheteroaryl of R⁵ is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); or asalt thereof.

A specific compound of the invention is a compound wherein at least oneZ is —N(R^(8y))—.

A specific compound of the invention is a compound wherein each Z is—N(R^(8y))—.

A specific compound of the invention is a compound wherein R^(8x) is(C₁-C₆)alkyl.

A specific compound of the invention is a compound wherein R⁶, R⁷, R⁸,R^(4′) and R^(5′) are each independently (C₁-C₃)alkoxy.

A specific compound of the invention is a compound wherein R⁶, R⁷, R⁸,R^(4′) and R^(5′) are each methoxy.

A specific compound of the invention is a compound wherein R⁸ is(C₁-C₃)alkoxy.

A specific compound of the invention is a compound wherein R⁸ ismethoxy.

A specific compound of the invention is a compound wherein R^(4′) is(C₁-C₃)alkoxy.

A specific compound of the invention is a compound wherein R^(4′) ismethoxy.

A specific compound of the invention is a compound wherein R^(5′) is(C₁-C₃)alkoxy.

A specific compound of the invention is a compound wherein R^(5′) ismethoxy.

A specific compound of the invention is a compound wherein R⁷, R⁸,R^(4′) and R^(5′) are each methoxy.

A specific compound of the invention is a compound wherein R⁷ and R⁸taken together are methylenedioxy.

A specific compound of the invention is a compound wherein R^(4′) andR^(5′) taken together are methylenedioxy.

A specific compound of the invention is a compound wherein R⁶ and R⁷taken together are methylenedioxy and R^(4′) and R^(5′) taken togetherare methylenedioxy.

A specific value for R⁸³ is cyano.

A specific value for R⁸³ is —NR^(a)R^(b).

A specific value for R^(8a) is hydrogen or methyl.

A specific value for R^(8b) is hydrogen, (C₁-C₆)alkyl, aryl,aryl(C₁-C₆)alkyl, heteroaryl, or heteroaryl(C₁-C₆)alkyl.

A specific value for R^(8b) is hydrogen, methyl, phenyl, or benzyl.

A specific value for R^(8b) is —C(═NR^(8c))—R^(8d).

A specific value for R^(8a) and R^(8b) taken together with the nitrogento which they are attached form aziridino, azetidino, morpholino,piperazino, pyrrolidino or piperidino, which aziridino, azetidino,morpholino, piperazino, pyrrolidino or piperidino can optionally besubstituted with one or more (C₁-C₆)alkyl.

A specific value for R^(8c) is hydrogen.

A specific value for R^(8d) is methyl or amino.

A specific value for R⁸³ is H.

A specific compound of the invention is a compound which is:

or a salt thereof.

A specific compound of the invention is a compound which is:

or a salt thereof.

A specific compound of the invention is a compound of formula (VIIIa)wherein R^(6′) is selected from aryl and heteroaryl, which aryl, andheteroaryl of R^(6′) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂ ⁸R^(k), and —NR^(8g)R^(8h); andeach R^(8aa) is independently selected from aryl and heteroaryl, whicharyl and heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIb)wherein R^(3′) is selected from aryl and heteroaryl, which aryl, andheteroaryl of R^(3′) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIc)wherein R^(2′) is selected from aryl and heteroaryl, which aryl, andheteroaryl of R^(2′) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIId)wherein R⁴ is selected from aryl and heteroaryl, which aryl, andheteroaryl of R⁴ is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIe)wherein R⁵ is selected from aryl and heteroaryl, which aryl, andheteroaryl of R⁵ is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIa)wherein R^(6′) is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g8)R^(h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (Ib)wherein R^(3′) is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIc)wherein R^(2′) is selected from aryl and heteroaryl, which aryl, andheteroaryl of R^(2′) is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(g)R^(h).

A specific compound of the invention is a compound of formula (VIIId)wherein R⁴ is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h)—N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIe)wherein R⁵ is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro, (C₁-C₆)alkoxy,cycloalkyl, carboxy, aryloxy, nitro, sulfo, R^(8aa),—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h); and eachR^(8aa) is independently selected from aryl and heteroaryl, which aryland heteroaryl is optionally substituted with one or more groupsindependently selected from (C₁-C₆)alkyl, halo, hydroxy, cyano, nitro,(C₁-C₆)alkoxy, cycloalkyl, carboxy, aryloxy, nitro, sulfo,—S(O)₂NR^(8g)R^(8h), —N(R^(8j))S(O)₂R^(8k), and —NR^(8g)R^(8h).

A specific compound of the invention is a compound of formula (VIIIa)wherein R^(6′) is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom phenyl, pyridyl, —NR^(8g)R^(8h), (C₁-C₆)alkoxy,dimethylaminophenyl, and halo.

A specific compound of the invention is a compound of formula (VIIIb)wherein R^(3′) is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom phenyl, pyridyl, —NR^(8g)R^(8h), (C₁-C₆)alkoxy,dimethylaminophenyl, and halo.

A specific compound of the invention is a compound of formula (VIIIc)wherein R^(2′) is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom phenyl, pyridyl, —NR^(8g)R^(8h), (C₁-C₆)alkoxy,dimethylaminophenyl, and halo.

A specific compound of the invention is a compound of formula (VIIId)wherein R⁴ is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom phenyl, pyridyl, —NR^(8g)R^(8h), (C₁-C₆)alkoxy,dimethylaminophenyl, and halo.

A specific compound of the invention is a compound of formula (VIIIe)wherein R⁵ is selected from phenyl, pyridyl and furanyl and isoptionally substituted with one or more groups independently selectedfrom phenyl, pyridyl, —NR^(8g)R^(8h), (C₁-C₆)alkoxy,dimethylaminophenyl, and halo.

A specific compound of the invention is a compound wherein at least oneof R⁴, R⁵, R^(2′), R^(3′), and R^(6′) is selected from 3-biphenyl,3-(4′-fluoro)biphenyl, 4-biphenyl, 4-(4′-fluoro)biphenyl,3,5-bis(4-fluorophenyl)phenyl, 4-fluorophenyl, phenyl, 3-pyridyl,4-pyridyl, 3-dimethylaminophenyl, 3-furanyl, 3-methoxyphenyl,4-pyrid-3-ylphenyl, 4-pyrid-4-ylphenyl, 4-(3-dimethylaminophenyl)phenyl,4-(3-furanyl)phenyl, 2-phenylpyrid-4-yl, 2-(3-methoxyphenyl)pyrid-3-yl,2-phenylfur-4-yl, and 2-pyrid-4-yl)pyrid-5-yl.

A specific compound of the invention is a compound wherein at least oneof R⁴, R⁵, R⁶, R⁷, R⁸, and R³¹ is selected from 3-biphenyl,3-(4′-fluoro)biphenyl, 4-biphenyl, 4-(4′-fluoro)biphenyl,3,5-bis(4-fluorophenyl)phenyl, 4-fluorophenyl, phenyl, 3-pyridyl,4-pyridyl, 3-dimethylaminophenyl, 3-furanyl, 3-methoxyphenyl,4-pyrid-3-ylphenyl, 4-pyrid-4-ylphenyl, 4-(3-dimethylaminophenyl)phenyl,4-(3-furanyl)phenyl, 2-phenylpyrid-4-yl, 2-(3-methoxyphenyl)pyrid-3-yl,2-phenylfur-4-yl, and 2-pyrid-4-yl)pyrid-5-yl.

A specific compound of the invention is a compound wherein at least oneof R⁴, R⁵, R⁶, and R⁷ is selected from 3-biphenyl,3-(4′-fluoro)biphenyl, 4-biphenyl, 4-(4′-fluoro)biphenyl,3,5-bis(4-fluorophenyl)phenyl, 4-fluorophenyl, phenyl, 3-pyridyl,4-pyridyl, 3-dimethylaminophenyl, 3-furanyl, 3-methoxyphenyl,4-pyrid-3-ylphenyl, 4-pyrid-4-ylphenyl, 4-(3-dimethylaminophenyl)phenyl,4-(3-furanyl)phenyl, 2-phenylpyrid-4-yl, 2-(3-methoxyphenyl)pyrid-3-yl,2-phenylfur-4-yl, and 2-pyrid-4-yl)pyrid-5-yl.

A specific compound of the invention is a compound wherein at least oneof R³, R⁴, R⁵, and R^(6′) is selected from 3-biphenyl,3-(4′-fluoro)biphenyl, 4-biphenyl, 4-(4′-fluoro)biphenyl,3,5-bis(4-fluorophenyl)phenyl, 4-fluorophenyl, phenyl, 3-pyridyl,4-pyridyl, 3-dimethylaminophenyl, 3-furanyl, 3-methoxyphenyl,4-pyrid-3-ylphenyl, 4-pyrid-4-ylphenyl, 4-(3-dimethylaminophenyl)phenyl,4-(3-furanyl)phenyl, 2-phenylpyrid-4-yl, 2-(3-methoxyphenyl)pyrid-3-yl,2-phenylfur-4-yl, and 2-pyrid-4-yl)pyrid-5-yl.

A specific value for A is N.

A specific value for A is C—R^(4′).

A specific compound of the invention is a compound which is:

or a salt thereof.

A specific value for B⁻ is Cl⁻, Br⁻, I⁻, CF₃SO₃ ⁻, malate, fumarate,formate, tosylate, methanesulfonate, acetate, citrate, malonate,tartrate, succinate, benzoate, ascorbate, α-ketoglutarate, orα-glycerophosphate.

A specific value for D⁻ is Cl⁻, Br⁻, I⁻, CF₃SO₃ ⁻, malate, fumarate,formate, tosylate, methanesulfonate, acetate, citrate, malonate,tartrate, succinate, benzoate, ascorbate, α-ketoglutarate, orα-glycerophosphate.

A specific value for Z⁻ is Cl⁻, Br⁻, I⁻, CF₃SO₃ ⁻, malate, fumarate,formate, tosylate, methanesulfonate, acetate, citrate, malonate,tartrate, succinate, benzoate, ascorbate, α-ketoglutarate, orα-glycerophosphate.

A specific value for B⁻ is: Cl⁻, Br⁻, I⁻, CH₃SO₃ ⁻, CF₃SO₃ ⁻, p-CH₃C₆H₄⁻SO₃ ⁻, citrate, tartrate, malate, fumarate, formate, or acetate.

A specific value for D⁻ is: Cl⁻, Br⁻, I⁻, CH₃SO₃ ⁻, CF₃SO₃ ⁻,p-CH₃C₆H₄SO₃ ⁻, citrate, tartrate, malate, fumarate, formate, oracetate.

A specific value for Z⁻ is: Cl⁻, Br⁻, I⁻, CH₃SO₃ ⁻, CF₃SO₃ ⁻,p-CH₃C₆H₄SO₃ ⁻, citrate, tartrate, malate, fumarate, formate, oracetate.

A specific compound of the invention is a compound wherein:

X is N; Y is C(R²); and R³ is R^(e); or

X is N; Y is C(R¹⁵); and R³ is R^(c); or

X is N⁺—R¹³ (Z⁻); Y is C(R¹²); and R³ is R^(c); or

X is N; Y is C(R¹²); and R³ is R^(e); or

X is W—R⁵¹; Y is C(R⁵²); W is N; and R^(51′) is absent; or

X is W—R⁵¹; Y is C(R⁵²); W is N⁺D⁻; and R⁵¹ is (C₁-C₆)alkyl, aryl, oraryl(C₁-C₆)alkyl; or

X is ⁺N(R⁸¹)(R⁸²) B⁻; and Y is C(R⁸³).

A specific compound of the invention is a compound wherein:

X is C(R¹); Y is N; and R³ is R^(c) or

X is C(R¹⁰) or C(R³¹); Y is N⁺—R¹⁴ (Z⁻); and R³ is R^(c); or

X is C(R¹⁰) or C(R³¹); Y is N; and R³ is R^(c).

A specific compound of the invention is a compound wherein:

X is C(R¹⁶); Y is C(R¹¹); and R³ is R^(e); or

X is C(R¹); Y is C(R¹²); and R³ is R^(e); or

X is C(R³⁰); Y is C(R³¹); and R³ is R^(e); or

X is W—R⁵¹; Y is C(R⁵²); W is C; and R⁵¹ is hydrogen, —N⁺(R^(5a))₃D⁻,—C(═NR^(5b))—NR^(5c)R^(5d), —NR^(e)—C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5g)R^(5h), —NR^(5ce)—C(═NR^(5cb))R^(5ce),—NR^(5ce)—C(═O)—NR^(5cc)R^(5cd), or (C₁-C₆)alkyl that is substitutedwith one or more R^(5f).

A specific compound of the invention is a compound wherein:

X is N; Y is C(R²); and R³ is R^(e); or

X is N; Y is C(R¹⁵); and R³ is R^(c); or

X is N⁺—R¹³ (Z⁻); Y is C(R¹²); and R³ is R^(c); or

X is N; Y is C(R¹²); and R³ is R^(e).

A specific compound of the invention is a compound wherein:

X is C(R¹); Y is N; and R³ is R^(c) or

X is C(R¹⁰) or C(R³¹); Y is N⁺—R¹⁴ (Z⁻); and R³ is R^(c); or

X is C(R¹⁰) or C(R³¹); Y is N; and R³ is R^(c).

A specific compound of the invention is a compound wherein:

X is C(R¹⁶); Y is C(R¹¹); and R³ is R^(e); or

X is C(R¹); Y is C(R¹²); and R³ is R^(e); or

X is C(R³⁰); Y is C(R³¹); and R³ is R^(e).

A specific compound of the invention is a compound of any one of theExamples hereinbelow or a salt or prodrug thereof.

Generally, compounds of the invention including compounds of formula Ias well as synthetic intermediates that can be used for preparingcompounds of formula I, can be prepared as illustrated in the followingSchemes. It is understood that variable groups (e.g. R¹-R¹⁵, A, W, X, Y,etc.) shown in the Schemes below can represent the final groups presentin a corresponding compound of formula I or that these groups canrepresent groups that can be converted to the final groups present in acorresponding compound of formula I at a convenient point in a syntheticsequence. For example, in the Schemes below, the variable groups cancontain one or more protecting groups that can be removed at aconvenient point in a synthetic sequence to provide the correspondingfinal groups in the compound of formula I.

When R⁴ is an aryl or heteroaryl substituent it can conveniently beintroduced into a compound of formula I as illustrated in Scheme 1.

When R⁵ is an aryl or heteroaryl substituent it can conveniently beintroduced into a compound of formula I as illustrated in Scheme 2.

When R⁶ is an aryl or heteroaryl substituent it can conveniently beintroduced into a compound of formula I as illustrated in Scheme 3.

When R⁷ is an aryl or heteroaryl substituent it can conveniently beintroduced into a compound of formula I as illustrated in Scheme 4.

A compound of formula I wherein X is N—R¹³ can conveniently be preparedfrom a corresponding compound wherein X is N as illustrated in Scheme 5.

A compound of formula I wherein Y is N—R¹⁴ can conveniently be preparedfrom a corresponding compound wherein Y is N as illustrated in Scheme 6.

Scheme 7 illustrates a general method for preparing 5-substituted2-(substituted phenyl)naphthalenes, 2-(pyridin-2-yl)naphthalenes, and2-(pyrimidin-2-yl)naphthalenes.

Scheme 8 illustrates a method for preparing various 5-substituted2-(phenyl)naphthalenes and 2-(heteroaryl)naphthalenes.

Scheme 9 illustrates a method for preparing 5-substituted2-(phenyl)naphthalenes and 2-(heteroaryl)naphthalenes.

Scheme 10 illustrates a method for the preparation of various4-substituted 2-phenylnaphthalenes and 2-(heteroaryl)naphthalenes.

Scheme 11 illustrates a method for the preparation of various4-substituted 2-(phenyl)naphthalenes or 4-substituted2-(heteroaryl)naphthalenes.

Scheme 12 illustrates a method for preparing 5-substituted2-[2-(dimethylamino)phenyl]-naphthalenes using the carbanion oftetralone and aryl halides.

Scheme 13 illustrates the use of 2-naphthyl boronates to form2-[2-amino)phenyl]- and 2-pyrimidinyl-naphthalene compounds.

Scheme 14 illustrates the use of 2-naphthyl boronates to form2-[2-amino)phenyl]- and 2-pyrimidinyl-naphthalene compounds.

Scheme 15 illustrates a method for preparing various 4-substituted2-phenyl-aminonaphthalenes usingsubstituted-1-amino-4-bromo-2-hydroxynaphthalenes as intermediates.

Scheme 16 illustrates a method for preparing various 5-substituted2-phenyl-aminonaphthalenes using substituted-1-nitro-5-bromonaphthalenesas intermediates.

Scheme 17 illustrates a method for preparing4-substituted-2-phenylquinolines using 2,4-dibromonaphthalenes.

Scheme 18 illustrates a method for preparing 4-aryl-2-phenylquinolinesusing 4-aryl-2-quinolones, which can be synthesized by a variety ofestablished methods.

Scheme 19 illustrates a method for preparing5-substituted-2-phenylquinolines with varied 6′-substituents from5-bromo-2-quinolinones.

Scheme 20 illustrates a method for preparing 5-substituted phenyl and5-substituted pyridyl 2-phenylquinolines with varied 6′-substituentsfrom 5-phenyl- and 5-(2-pyridyl)-2-quinolinones.

Scheme 21 illustrates a method for varying substituents at theR^(56′)-position by incorporation of a R^(56′)-protected phenol withinan organoboronate that can be used to prepare various compounds asexemplified for 2-(2′-aminophenyl)naphthalene analogs.

Scheme 22 illustrates a method for varying substituents at theR^(56′)-position by incorporation of a R^(56′)-phenyl within anorganoboronate that can be used to prepare various compounds asexemplified for 2-(3′-phenylpyridin-2′-yl)naphthalene analogs.

Scheme 23 illustrates a general method for the preparation of3-phenylquinoline and 1-alkyl-3-phenylquinolinium compounds with varied3′-substituents.

Scheme 24 illustrates a method for the preparation of substituted3′phenyl-4′,5′-dimethoxyphenyl-6,7-dimethoxy-3-phenylquinoline compoundsand their methylquinolinium iodide derivatives.

Scheme 25 illustrates a general method for the preparation ofsubstituted3′phenyl-4′,5′-dimethoxyphenyl-6,8-dimethoxy-3-phenylquinoline compoundsand their methylquinolinium iodide derivatives.

Scheme 26 illustrates a general method for the preparation ofsubstituted3′-phenyl-4′,5′-dimethoxyphenyl-6,7-dimethoxy-3,4-diphenylquinolinecompounds and their methylquinolinium iodide derivatives.

Scheme 27 illustrates a general method for the preparation ofsubstituted3′-phenyl-4′,5′-dimethoxyphenyl-6,7-dimethoxy-3,5-diphenylquinolinecompounds and their methylquinolinium iodide derivatives.

Scheme 28 illustrates a general method for the preparation ofsubstituted 2-substituted 3,4,9,10-tetramethoxybenzo[a]acridines andtheir 7-methylbenzo[a]acridinium derivatives.

By binding to FtsZ, the compounds of the present invention inhibit theability of the protein to hydrolyze GTP. This inhibition of FtsZ GTPaseactivity, in turn, inhibits the ability of the protein to polymerizeinto Z-rings, as Z-ring formation requires GTP hydrolysis as an energysource for driving the reaction. Since the Z-ring serves as the scaffoldfor recruitment of all other proteins that comprise the divisomecomplex, inhibition of Z-ring formation by the compounds of the presentinvention also results in a corresponding inhibition of divisome proteinrecruitment.

The compounds of the invention are useful to treat bacterial infectionsincluding infections by Gram-negative bacterial strains, Gram-positivebacterial strains and multiple drug-resistant bacterial strains

Gram-negative bacterial strains include Escherchia coli, Caulobactercrescentus, Pseudomonas aeruginosa, Agrobacterium tumefaciens,Branhamella catarrhalis, Citrobacter diversus, Enterobacter aerogenes,Enterobacter cloacae, Enterobacter sakazakii, Enterobacter asburiae,Pantoea agglomerans, Klebsiella pneumoniae, Klebsiella oxytoca,Klebsiella rhinoscleromatis, Proteus mirabilis, Salmonella typhimurium,Salmonella enteriditis, Serratia marcescens, Shigella sonnei, Neisseriagonorrhoeae, Acinetobacter baumannii, Acinetobacter calcoaceticus,Acinetobacter lwoffi, Fusobacterium nucleatum, Veillonella parvula,Bacteroides forsythus, Actinobacillus actinomycetemcomitans,Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis,Helicobacter pylori, Francisella tularensis, Yersinia pestis, Borreliaburgdorferi, Neisseria meningitidis and Haemophilus influenza.

Gram-positive bacterial strains include Staphylococcus aureus,Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcuspyogenes, Streptococcus faecalis, Enterococcus faecalis, Enterococcusfaecium, Bacillus subtilis, Bacillus anthracis, Bacillus cereus,Micrococcus luteus, Mycobacterium tuberculosis, Clostridium difficile,Propionibacterium acnes, Streptococcus mutans, Actinomyces viscosus,Actinomyces naeslundii, Streptococcus sanguis, Streptococcus pneumoniae,Streptococcus viridans and Streptococcus salivarius.

Multiple drug-resistant bacterial strains include methicillin-resistantStaphylococcus aureus, vancomycin-resistant Enterococci, multipledrug-resistant Mycobacterium tuberculosis, and multidrug-resistantClostridium difficile.

In one embodiment compounds of the present invention may be administeredas a composition used to treat and/or prevent a bacterial infectionwherein the bacterial cell uses polymerized FtsZ protein, or a homologthereof, to facilitate cytokinesis. To this end, compounds of thepresent invention may be administered to treat Staph Infections,Tuberculosis, Urinary Tract Infections, Meningitis, Enteric Infections,Wound Infections, Acne, Encephalitis, Skin Ulcers, Bed Sores, Gastricand Duodenal Ulcers, Eczema, Periodontal disease, Gingivitis, Halitosis,Anthrax, Tularemia, Endocarditis, Prostatitis, Osteomyelitis, LymeDisease, Pneumonia, or the like.

The compositions can, if desired, also contain other active therapeuticagents, such as a narcotic, a non-steroid anti-inflammatory drug(NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, aneuromuscular blocker, an anti-cancer, other antimicrobial (for example,an aminoglycoside, an antifungal, an antiparasitic, an antiviral, acarbapenem, a cephalosporin, a fluororquinolone, a macrolide, apenicillin, a sulfonamide, a tetracycline, another antimicrobial), ananti-psoriatic, a corticosteriod, an anabolic steroid, adiabetes-related agent, a mineral, a nutritional, a thyroid agent, avitamin, a calcium-related hormone, an antidiarrheal, an anti-tussive,an anti-emetic, an anti-ulcer, a laxative, an anticoagulant, anerythropieitin (for example, epoetin alpha), a filgrastim (for example,G-CSF, Neupogen), a sargramostim (GM-CSF, Leukine), an immunization, animmunoglobulin, an immunosuppressive (for example, basiliximab,cyclosporine, daclizumab), a growth hormone, a hormone replacement drug,an estrogen receptor modulator, a mydriatic, a cycloplegic, analkylating agent, an anti-metabolite, a mitotic inhibitor, aradiopharmaceutical, an anti-depressant, an anti-manic agent, ananti-psychotic, an anxiolytic, a hypnotic, a sympathomimetic, astimulant, donepezil, tacrine, an asthma medication, a beta agonist, aninhaled steroid, a leukotriene inhibitor, a methylxanthine, a cromolyn,an epinephrine or analog thereof, dornase alpha (Pulmozyme), a cytokine,or any combination thereof.

The term “prodrug” as used herein refers to any compound that whenadministered to a biological system (e.g. a mammal such as a human)generates the drug substance, i.e. active ingredient, as a result ofspontaneous chemical reaction(s), enzyme catalyzed chemical reaction(s),photolysis, and/or metabolic chemical reaction(s) or by some otherprocess. A prodrug is thus a modified (e.g. covalently modified) analogor latent form of a therapeutically-active compound. A prodrug may alsobe an active metabolite or therapeutically-active compound itself.

By way of example a prodrug may generate the active inhibitory compoundduring metabolism, systemically, inside a cell, by hydrolysis, enzymaticcleavage, or by some other process (Bundgaard, Hans, “Design andApplication of Prodrugs” in A Textbook of Drug Design and Development(1991), P. Krogsgaard-Larsen and H. Bundgaard, Eds. Harwood AcademicPublishers, pp. 113-191; Tranoyl-Opalinski, I., Fernandes, A., Thomas,M., Gesson, J.-P., and Papot, S., Anti-Cancer Agents in Med. Chem., 8(2008) 618-637). Enzymes which are capable of an enzymatic activationmechanism with the prodrug compounds of the invention include, but arenot limited to nitroreductase, proteases (e.g. serine proteases such asprostate specific antigen (PSA), amidases, esterases, microbial enzymes,phospholipases, cholinesterases, and phosphases).

Processes for preparing compounds of formula I are provided as furtherembodiments of the invention and are illustrated by the followingprocedures in which the meanings of the generic radicals are as givenabove unless otherwise qualified.

In cases where compounds are sufficiently basic or acidic, a salt of acompound of formula I can be useful as an intermediate for isolating orpurifying a compound of formula I. Additionally, administration of acompound of formula I as a pharmaceutically acceptable acid or base saltmay be appropriate. Examples of pharmaceutically acceptable salts areorganic acid addition salts formed with acids which form a physiologicalacceptable anion, for example, tosylate, methanesulfonate, acetate,citrate, malonate, tartrate, succinate, benzoate, ascorbate,α-ketoglutarate, and α-glycerophosphate. Suitable inorganic salts mayalso be formed, including hydrochloride, sulfate, nitrate, bicarbonate,and carbonate salts. Salts may be obtained using standard procedureswell known in the art, for example by reacting a sufficiently basiccompound such as an amine with a suitable acid affording thecorresponding anion. Alkali metal (for example, sodium, potassium orlithium) or alkaline earth metal (for example calcium) salts ofcarboxylic acids can also be made.

Pharmaceutically suitable counterions include pharmaceutically suitablecations and pharmaceutically suitable anions that are well known in theart. Examples of pharmaceutically suitable anions include, but are notlimited to those described above (e.g. physiologically acceptableanions) including Cl⁻, Br⁻, I⁻, CH₃SO₃ ⁻, CF₃SO₃ ⁻, p-CH₃C₆H₄SO₃ ⁻,citrate, tartrate, malate, fumarate, formate, or acetate.

It will be appreciated by those skilled in the art that a compound ofthe invention comprising a counterion can be converted to a compound ofthe invention comprising a different counterion. Such a conversion canbe accomplished using a variety of well known techniques and materialsincluding but not limited to ion exchange resins, ion exchangechromatography and selective crystallization.

The compounds of formula I can be formulated as pharmaceuticalcompositions and administered to a mammalian host, such as a humanpatient in a variety of forms adapted to the chosen route ofadministration, i.e., orally or parenterally, by intravenous,intramuscular, topical or subcutaneous routes.

Thus, the present compounds may be systemically administered, e.g.,orally, in combination with a pharmaceutically acceptable vehicle suchas an inert diluent, excipient or an assimilable edible carrier. Theymay be enclosed in hard or soft shell gelatin capsules, may becompressed into tablets, or may be incorporated directly with the foodof the patient's diet. For oral therapeutic administration, the activecompound may be combined with one or more excipients and used in theform of ingestible tablets, buccal tablets, troches, capsules, elixirs,suspensions, syrups, wafers, and the like. Such compositions andpreparations should contain at least 0.1% of active compound. Thepercentage of the compositions and preparations may, of course, bevaried and may conveniently be between about 2 to about 90% of theweight of a given unit dosage form. The amount of active compound insuch therapeutically useful compositions is such that an effectivedosage level will be obtained.

The tablets, troches, pills, capsules, and the like may also contain thefollowing: binders such as gum tragacanth, acacia, corn starch orgelatin; excipients such as dicalcium phosphate; a disintegrating agentsuch as corn starch, potato starch, alginic acid and the like; alubricant such as magnesium stearate; and a sweetening agent such assucrose, fructose, lactose or aspartame or a flavoring agent such aspeppermint, oil of wintergreen, or cherry flavoring may be added. Whenthe unit dosage form is a capsule, it may contain, in addition tomaterials of the above type, a liquid carrier, such as a vegetable oilor a polyethylene glycol. Various other materials may be present ascoatings or to otherwise modify the physical form of the solid unitdosage form. For instance, tablets, pills, or capsules may be coatedwith gelatin, wax, shellac or sugar and the like. A syrup or elixir maycontain the active compound, sucrose or fructose as a sweetening agent,methyl and propylparabens as preservatives, a dye and flavoring such ascherry or orange flavor. Of course, any material used in preparing anyunit dosage form should be pharmaceutically acceptable and substantiallynon-toxic in the amounts employed. In addition, the active compound maybe incorporated into sustained-release preparations, particles, anddevices.

The active compound may also be administered intravenously orintramuscularly by infusion or injection. Solutions of the activecompound or its salts can be prepared in water, optionally mixed with anontoxic surfactant. Dispersions can also be prepared in glycerol,liquid polyethylene glycols, triacetin, and mixtures thereof and inoils. Under ordinary conditions of storage and use, these preparationscontain a preservative to prevent the growth of microorganisms.

The pharmaceutical dosage forms suitable for injection or infusion caninclude sterile aqueous solutions or dispersions or sterile powderscomprising the active ingredient which are adapted for theextemporaneous preparation of sterile injectable or infusible solutionsor dispersions, optionally encapsulated in liposomes. In all cases, theultimate dosage form should be sterile, fluid and stable under theconditions of manufacture and storage. The liquid carrier or vehicle canbe a solvent or liquid dispersion medium comprising, for example, water,ethanol, a polyol (for example, glycerol, propylene glycol, liquidpolyethylene glycols, and the like), vegetable oils, nontoxic glycerylesters, and suitable mixtures thereof. The proper fluidity can bemaintained, for example, by the formation of liposomes, by themaintenance of the required particle size in the case of dispersions orby the use of surfactants. The prevention of the action ofmicroorganisms can be brought about by various antibacterial andantifungal agents, for example, parabens, chlorobutanol, phenol, sorbicacid, thimerosal, and the like. In many cases, it will be preferable toinclude isotonic agents, for example, sugars, buffers or sodiumchloride. Prolonged absorption of the injectable compositions can bebrought about by the use in the compositions of agents delayingabsorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions are prepared by incorporating the activecompound in the required amount in the appropriate solvent with variousof the other ingredients enumerated above, as required, followed byfilter sterilization. In the case of sterile powders for the preparationof sterile injectable solutions, the preferred methods of preparationare vacuum drying and the freeze drying techniques, which yield a powderof the active ingredient plus any additional desired ingredient presentin the previously sterile-filtered solutions.

For topical administration, the present compounds may be applied in pureform, i.e., when they are liquids. However, it will generally bedesirable to administer them to the skin as compositions orformulations, in combination with a dermatologically acceptable carrier,which may be a solid or a liquid.

Useful solid carriers include finely divided solids such as talc, clay,microcrystalline cellulose, silica, alumina, nanoparticles, and thelike. Useful liquid carriers include water, alcohols or glycols orwater-alcohol/glycol blends, in which the present compounds can bedissolved or dispersed at effective levels, optionally with the aid ofnon-toxic surfactants. Adjuvants such as fragrances and additionalantimicrobial agents can be added to optimize the properties for a givenuse. The resultant liquid compositions can be applied from absorbentpads, used to impregnate bandages and other dressings, or sprayed ontothe affected area using pump-type or aerosol sprayers.

Thickeners such as synthetic polymers, fatty acids, fatty acid salts andesters, fatty alcohols, modified celluloses or modified mineralmaterials can also be employed with liquid carriers to form spreadablepastes, gels, ointments, soaps, and the like, for application directlyto the skin of the user.

Useful dosages of the compounds of formula I can be determined bycomparing their in vitro activity, and in vivo activity in animalmodels. Methods for the extrapolation of effective dosages in mice, andother animals, to humans are known to the art; for example, see U.S.Pat. No. 4,938,949.

The amount of the compound, or an active salt or derivative thereof,required for use in treatment will vary not only with the particularsalt selected but also with the route of administration, the nature ofthe condition being treated and the age and condition of the patient andwill be ultimately at the discretion of the attendant physician orclinician.

In general, however, a suitable dose will be in the range of from about0.1 to about 500 mg/kg, e.g., from about 0.5 to about 400 mg/kg of bodyweight per day, such as 1 to about 250 mg per kilogram body weight ofthe recipient per day.

The compound is conveniently formulated in unit dosage form; forexample, containing 0.5 to 500 mg, 1 to 400 mg, or 0.5 to 100 mg ofactive ingredient per unit dosage form. In one embodiment, the inventionprovides a composition comprising a compound of the invention formulatedin such a unit dosage form.

The desired dose may conveniently be presented in a single dose or asdivided doses administered at appropriate intervals, for example, astwo, three, four or more sub-doses per day. The sub-dose itself may befurther divided, e.g., into a number of discrete loosely spacedadministrations.

The ability of a compound of the invention to alter the polymerizationdynamics of FtsZ can be determined using a method like Test A describedbelow.

Test A. Determining the Impact of the Compounds of the Invention on FtsZPolymerization Dynamics.

Compound-induced alteration in FtsZ polymerization dynamics can betested using a light scattering-based competition binding assay usingpurified FtsZ. Upon addition of GTP, FtsZ self-associates to formpolymeric structures that scatter light at 340 nm to a greater extentthan the monomeric protein. The impact of the compounds of the inventionon the polymerization dynamics of FtsZ can be detected by an increase ofdecrease in the extent of GTP-induced light scattering relative to thatobserved in the absence of compound. Quantitation of the overall extentof light scattering as a function of compound concentration to yield acompound concentration at which FtsZ polymerization is inhibited by 50%(IC₅₀) provides an indication of the potency of that compound ataltering FtsZ polymerization dynamics.

The ability of a compound of the invention to inhibit FtsZ GTPaseactivity can be determined using a method like Test B described below.

Test B. Determining the FtsZ GTPase Inhibitory Activities of Compoundsof the Invention.

Compound-induced inhibition of the FtsZ GTPase activity can be testedusing a colorimetric assay in which the inorganic phosphate (P_(i))released upon FtsZ-catalyzed hydrolysis of GTP reacts with malachitegreen and molybdate under acidic conditions to form a ternary complexthat absorbs light at 650 nm, thus enabling quantitation of P_(i) levelsby recording the absorbance at 650 nm (A₆₅₀). Differing concentrationsof test compound are combined with GTP and the reactions (run intriplicate) are initiated by addition of FtsZ. After incubation for 60minutes at room temperature, the reactions are stopped by addition of anacidic malachite green-molybdate solution containing malachite greenoxalate, sodium molybdate, Triton X-100, and 0.7 N HCl. For the purposesof generating a standard curve, each experiment includes reactionscontaining known concentrations of monobasic potassium phosphate(KH₂PO₄) in place of FtsZ. Ten minutes following addition of the acidicmalachite green-molybdate solution, the A₆₅₀ value for each reaction isrecorded. A standard curve of A₆₅₀ versus P_(i) concentration isconstructed using the average A₆₅₀ value obtained for each known KH₂PO₄concentration. This standard curve is then fit by linear regressionanalysis to yield the quantitative relationship between A₆₅₀ and P_(i)concentration. The resulting relationship as well as the average A₆₅₀value for each test reaction is used to calculate the concentrations ofP_(i) released by the GTPase activity of FtsZ. The released P_(i)concentration in the absence of test compound is set as the mark for100% GTPase activity, and is used to calculate the percent GTPaseactivities in reactions containing test compounds. The percent GTPaseactivity is then plotted as a function of log (compound concentration),with the resulting curves being fit using an appropriate sigmoidalrelationship to obtain the compound concentrations at which GTPaseactivity is inhibited by 50% (IC₅₀ values). These IC₅₀ values providequantitative measures of the potencies with which the test compounds ofthe invention inhibit FtsZ GTPase activity.

TABLE 1 Minimal Inhibitory Concentrations against MSSA forrepresentative compounds of the Invention MIC vs MSSA MIC vs MRSAExample Structure (ug/ml) (ug/ml) Example 2

≦8.0 — Example 4

16.0 — Example 6

≦8.0 — Example 8

≦8.0 — Example 11

≦8.0 ≦8.0 Example 13

≦8.0 — Example 14

≦8.0 — Example 16

≦8.0 — Example 19

≦8.0 ≦8.0 Example 21

≦8.0 — Example 22

≦8.0 — Example 25

≦8.0 — Example 26a

≦8.0 — Example 28

≦8.0 — Example 30

≦8.0 — Example 31

≦8.0 — Example 33

≦8.0 — Example 35

≦8.0 ≦8.0 Example 36

≦8.0 ≦8.0 Example 37

≦8.0 ≦8.0 Example 38

≦8.0 — Example 39

≦8.0 — Example 40

≦8.0 — Example 41

≦8.0 ≦8.0 Example 42

≦8.0 ≦8.0 Example 43

≦8.0 — Example 44

≦8.0 — Example 45

≦8.0 — Example 46

≦8.0 — Example 47

≦8.0 — Example 50

≦8.0 — Example 51

≦8.0 — Example 52

≦8.0 — Example 53

≦8.0 — Example 55

≦8.0 — Example 56

≦8.0 ≦8.0 Example 58

≦8.0 — Example 59

≦8.0 ≦8.0 Example 60

32.0 — Example 61

≦8.0 ≦8.0 Example 62

≦8.0 ≦8.0 Example 63

≦8.0 ≦8.0 Example 65

≦8.0 — Example 67

≦8.0 — Example 69

≦8.0 — Example 70

≦8.0 ≦8.0 Example 71

≦8.0 — Example 72

≦8.0 — Example 74

≦8.0 — Example 76

≦8.0 — Example 78

≦8.0 — Example 80

≦8.0 — Example 82

≦8.0 — Example 84

≦8.0 — Example 85

≦8.0 — Example 86

≦8.0 — Example 87

≦8.0 — Example 88

>64.0  — Example 89

≦8.0 — Example 93

≦8.0 — Example 95

≦8.0 — Example 97

≦8.0 — Example 100

≦8.0 — Example 101

≦8.0 — Example 102

≦8.0 — Example 103

≦8.0 — Example 104

≦8.0 — Example 105

≦8.0 — Example 106

≦8.0 — Example 107

≦8.0 — Example 112

≦8.0 32   Example 114

≦8.0 ≦8.0 Example 116

≦8.0 16   Example 118

16.0 — Example 120

≦8.0 >32    Example 122

≦8.0 — Comparative Example A

>64.0  — Comparative Example B

>64.0  —

The antibacterial activity of a compound of the invention can bedetermined using a method like Test C described below.

Test C. Planktonic (Free-Living) Antibacterial Assay.

Planktonic antibacterial activity can be determined using a brothmicrodilution assay in which log-phase bacteria are grown at 37° C. inappropriate medium containing two-fold serial dilutions of a compound toyield a final concentration ranging from 256 to 0.1 μg/ml. Fordetermination of minimal inhibitory concentration (MIC) values,bacterial growth is monitored after 24 to 48 hours by measuring opticaldensity at 600 nm. MIC values reflect the minimal compoundconcentrations at which bacterial growth is completely inhibited. Theminimal inhibitory concentration against methicillin-sensitiveStaphylococcus aureus (MSSA) for each of the following representativecompounds of the invention was determined to be less than 32 μg/ml.

TABLE 2 Inhibition of S. aureus FtsZ Polymerization and GTPase Activityby Representative Compounds of the Invention Compound ¹IC₅₀ (μg/mL)Example 19 <50 Example 41 <50 Example 42 <50 Example 63 <50 Example 104<50 Example 112 <50 Example 114 <50 Example 120 <50 ¹IC₅₀ reflects thecompound concentration at which FtsZ polymerization and/or GTPaseactivity is inhibited by 50%.

Representative compounds of the invention were also tested againstmethicillin-resistant Staphylococcus aureus, vancomycin-resistantEnterococcus faecalis and Enterococcus faecium (VRE),vancomycin-sensitive Enterococcus faecalis and Enterococcus faecium(VSE). Streptococcus pyogenes, Streptococcus agalactiae, Clostridiumdifficile, Propionibacterium acnes, Bacillus subtilis, and Escherichiacoli, and they were found to have significant antibacterial activity.

The invention will now be illustrated by the following non-limitingexamples.

EXAMPLES

The following general methods A-C can be used to prepare compounds ofthe invention.

General Methods of Preparation

A. Suzuki Reaction

A mixture of either the aryl triflate or aryl bromide (commerciallyavailable), appropriate boronic acid (2 equiv.), Cs₂CO₃, Pd (PPh₃)₂Cl₂(5 mol %) in dioxane was micro waved for 15 minutes. The crude reactionmixture was diluted with ethyl acetate and was filtered through a plugof Celite and silica gel. The filtrate was concentrated under vacuo andwas subjected to flash column chromatography to afford the desiredproduct.

B. Quaternization

The starting material (approx. 100 mg-150 mg) was dissolved in methyliodide (1.5 ml-2 ml) in a sealed tube and was heated at 80° C. for 15-30minutes. The resulting solid was then diluted with acetone, filtered andwashed with diethyl ether twice to afford the quaternary salts as puresolids.

C. Triflation Reaction

The required hydroxyl compound was dissolved in dichloromethane to whichadded 2.0 equivalent of triethylamine and 1.5 equivalent of Tf₂O at −78°C. After the reaction is completed, the reaction mixture was dilutedwith more methylene chloride which was then washed with saturated sodiumbicarbonate and brine. The crude mixture was then purified by flashcolumn chromatography to afford the product.

Example 1 Preparation of Compound

To a nitrogen-flushed mixture of 2,3-dimethoxy-5-(quinolin-3-yl)phenyltrifluoroethanesulfonate (0.10 g, 0.24 mmol), bi-phenylboronic acid (72mg, 0.36 mmol) and potassium carbonate (83 mg, 0.60 mmol) in a mixtureof acetonitrile (8 mL) and water (2 mL) at room temperature undernitrogen were added palladium acetate (3 mg, 0.013 mmol) and Xphos (13mg, 0.027 mmol), the resultant mixture was heated at 90° C. for 2 h. Itwas dried over MgSO₄, filtered and concentrated to a crude product.Purification by flash chromatography (SiO₂, EtOAc/hexane 0-50%) gave thedesired product as a pale oil (46 mg, 54%). ¹H NMR (CDCl₃, 400 MHz) δ:3.65 (s, 3H), 3.97 (s, 3H), 6.91 (s, 1H), 7.28 (m, 2H), 7.40 (m, 2H),7.52 (t, J=8.0 Hz, 1H), 7.59-7.68 (m, 7H), 7.82 (d, J=8.0 Hz, 1H), 8.08(d, J=8.0 Hz, 1H), 8.25 (s, 1H), 9.14 (s, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a nitrogen-flushed mixture of triisopropylborate (4.6 mL, 20 mmol),(3-(benzyloxy)-4,5-dimethoxy)bromobenzene (5.20 g, 16.1 mmol) in amixture of THF (40 mL) and toluene (160 mL) at −78° C. under nitrogenwas added dropwise n-BuLi (1.0 M/THF, 13 mL) over 25 min. The resultantmixture was stirred at −78° C. for 1 h, slowly warmed up to −50° C. andquenched with 2N HCl (20 mL). The reaction mixture was stirred at roomtemperature for 1 h. The organic layer was sepatated and diluted withEtOAc (100 mL), washed with brine twice and dried over Na₂SO₄, filteredand concentrated. The crude oil slowly solidified and treated with CH3CNto give a soft solid as the desired product. The mother liquid waspurified with flash column (SiO₂, MeOH/CH₂Cl₂, 0-5%) to give the desiredproduct. The total yield of combined product was 3.52 g (75%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.97 (s, 6H), 5.25 (s, 2H), 7.31.

b. Preparation of Compound

To a nitrogen-flushed mixture of 3-bromoquinoline (0.50 mL, 3.7 mmol),(3-(benzyloxy)-4,5-dimethoxyphenyl)boronic acid (1.26 g, 4.37 mmol) andpotassium carbonate (2.0 g, 14.5 mmol) in a mixture of dioxane (25 mL)and water (5 mL) at room temperature under nitrogen was addedtetrakis(triphenylphosphine)palladium (0.20 g, 0.17 mmol), the resultantmixture was heated at 100° C. for 4 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-30%) to give the desired product as a pale oil (1.33 g, 96%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.96 (s, 3H), 3.97 (s, 3H), 5.25 (s, 2H), 6.90 (dd,J=12.0 Hz, 4.0 Hz, 2H), 7.33 (m, 1H), 7.38-7.41 (m, 2H), 7.49 m, 2H),7.58 (m, 1H), 7.87 (d, J=8.0 Hz, 1H), 8.13 (d, J=8.0 Hz, 1H), 8.19 (s,1H), 9.07 (m, 1H).

c. Preparation of Compound

A mixture of 3-(3-(benzyloxy)-45-dimethoxyphenyl)quinoline (1.30 g, 3.5mmol) and 10% palladium on carbon (0.39 g, 30% w/w) was stirred at roomtemperature under 1 atm of hydrogen for 2 days. The catalyst wasfiltered off and the filtrate concentrated to an oil. Purification byflash chromatography (SiO₂, EtOAc/hexane 10-70%) gave the desiredproduct as a white solid (0.97 g, 99%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.98(s, 6H), 6.03 (s, 1H), 6.79 (s, 1H), 6.96 (s, 1H), 7.58 (t, J=8.0 Hz,1H), 7.70-7.74 (m, 1H), 7.87 (d, J=8.0 Hz, 1H), 8.13 (d, J=8.0 Hz, 1H),8.25 (s, 1H), 9.14 (s, 1H).

d. Preparation of Compound

To a solution of 2,3-dimethoxy-5-(quinolin-3-yl)phenol (0.48 g, 1.7mmol) and triethylamine (0.47 mL, 3.8 mmol) in CH₂Cl₂ (20 mL) at −78° C.under nitrogen was added triflate anhydride (0.36 mL, 2.1 mmol) slowly,the resultant mixture was stirred at −78° C. and warmed up to 0° C. Thereaction was diluted with methylenechloride to 50 mL and washed with aq.NaHCO₃ solution. The organic solution was dried over MgSO₄ andconcentrated to an oil. Purification by flash chromatography (SiO₂,EtOAc/hexane 10-50%) gave the desired product as an oil (0.26 g, 37%).¹H NMR (CDCl₃, 400 MHz) δ: 3.95 (s, 3H), 3.98 (s, 3H), 7.08-7.15 (m,1H), 7.20 (s, 1H), 7.59 (t, J=8.0 Hz, 1H) 7.73 (t, J=8.0 Hz, 1H), 7.86(d, J=8.0 Hz, 1H), 8.17 (d, J=8.0 Hz, 1H), 8.24 (s, 1H), 9.05 (s, 1H).

Example 2 Preparation of Compound

A mixture of 3-(4′-fluoro-5,6-dimethoxy-[1,1′-biphenyl]-3-yl)quinoline(45 mg, 0.13 mmol) in iodomethane (1 mL) was heated at 60° C. undernitrogen for 15 h. The reaction mixture was concentrated to dryness. Theresidue was treated with Et₂O. A yellow solid was collected to give thedesired product (51 mg, 80%). ¹H NMR (DMSO, 400 MHz) δ: 3.77 (s, 3H),4.12 (s, 3H), 4.78 (s, 3H), 7.46 (m, 1H), 7.57 (t, J=8.0 Hz, 2H),7.73-7.88 (m, 8H), 8.15 (t, J=8.0 Hz, 1H), 8.33 (t, J=8.0 Hz, 1H), 8.55(dd, J=12.0 Hz, 8.0 Hz, 2H), 9.77 (s, 1H), 10.1 (s, 1H).

Example 3 Preparation of Compound

To a nitrogen-flushed mixture of 2,3-dimethoxy-5-(quinolin-3-yl)phenyltrifluoromethanesulfonate (0.12 g, 0.29 mmol), 4-fluorophenylboronicacid (61 mg, 0.44 mmol) and potassium carbonate (0.1 g, 0.72 mmol) in amixture of acetonitrile (12 mL) and water (2 mL) at room temperatureunder nitrogen were added palladium acetate (3 mg, 0.013 mmol) and Xphos(13 mg, 0.027 mmol), the resultant mixture was heated at 90° C. for 2 h.It was dried over MgSO₄, filtered and concentrated to a crude product.Purification by flash chromatography (SiO₂, EtOAc/hexane 0-50%) gave thedesired product as a pale oil (76 mg, 88%). ¹H NMR (CDCl₃, 400 MHz) δ:3.59 (s, 3H), 3.96 (s, 3H), 7.07 (t, J=8.0 Hz, 2H), 7.16 (m, 2H),7.50-7.54 (m, 3H), 7.81 (m, 1H), 8.07 (d, J=8.0 Hz, 1H), 8.22 (s, 1H),9.11 (s, 1H).

Example 4 Preparation of Compound

The compound of Example 3 (70 mg, 0.24 mmol) in iodomethane (1.5 mL) washeated at 60° C. under nitrogen for overnight. The reaction mixture wasconcentrated to dryness. The residue was treated with Et₂O. A yellowsolid was collected to give the desired product (79 mg, 77%). ¹H NMR(DMSO, 400 MHz) δ: 3.72 (s, 3H), 4.10 (s, 3H), 4.77 (s, 3H), 7.41 (t,J=8.0 Hz, 2H), 7.68-7.78 (m, 3H), 7.79 (s, 1H), 8.15 (t, J=8.0 Hz, 1H),8.34 (t, J=8.0 Hz, 1H), 8.52 (d, J=8.0 Hz, 1H), 8.58 (d, J=8.0 Hz, 1H),9.75 (s, 1H), 10.05 (s, 1H).

Example 5 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate d in Example1,2,3-dimethoxy-5-(quinolin-3-yl)phenyl trifluoromethanesulfonate, (0.12g, 0.29 mmol), 3(4-fluorophenyl)phenylboronic acid (0.10 g, 0.46 mmol)and potassium carbonate (0.1 g, 0.72 mmol) in a mixture of acetonitrile(8.5 mL) and water (1.5 mL) at room temperature under nitrogen wereadded palladium acetate (5 mg, 0.022 mmol) and Xphos (20 mg, 0.042mmol), the resultant mixture was heated at 90° C. for 2 h. It was driedover MgSO₄, filtered and concentrated to a crude product. Purificationby flash chromatography (SiO₂, EtOAc/hexane 10-50%) gave the desiredproduct as a pale oil (16 mg, 13%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.59 (s,3H), 3.96 (s, 3H), 7.07 (t, J=8.0 Hz, 2H), 7.17 (m, 2H), 7.50-7.54 (m,3H), 7.65 (t, J=8.0 Hz, 1H), 7.81 (d, J=8.0 Hz, 1H), 8.07 (d, J=8.0 Hz,1H), 8.22 (d, J=4.0 Hz, 1H), 9.1 (s, 1H).

Example 6 Preparation of Compound

The compound of Example 5 (15 mg, 0.03 mmol) in iodomethane (0.35 mL)was heated at 60° C. under nitrogen for overnight. The reaction mixturewas concentrated to dryness. The residue was treated with Et₂O. A yellowsolid was collected to give the desired product (20 mg, 100%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.71 (s, 3H), 4.06 (s, 3H), 4.71 (s, 3H), 7.32 (t,J=8.0 Hz, 2H), 7.59 (d, J=4.0 Hz, 2H), 7.70-7.81 (m, 5H), 8.08 (t, J=8.0Hz, 1H), 8.26 (t, J=8.0 Hz, 1H), 8.48 (dd, J=24.0 Hz, 8.0 Hz, 2H), 9.7(s, 1H), 10.0 (s, 1H).

Example 7 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate d in Example 1 (0.12 g,0.29 mmol), bis-3,5-(4-fluorophenyl)phenylboronic acid (0.13 g, 0.42mmol) and potassium carbonate (0.1 g, 0.72 mmol) in a mixture ofacetonitrile (8.5 mL) and water (1.5 mL) at room temperature undernitrogen were added palladium acetate (5 mg, 0.022 mmol) and Xphos (20mg, 0.042 mmol), the resultant mixture was heated at 90° C. for 2 h. Itwas dried over MgSO₄, filtered and concentrated to a crude product.Purification by flash chromatography (SiO₂, EtOAc/hexane 10-50%) gavethe desired product as a pale oil (108 mg, 70%). ¹H NMR (CDCl₃, 400 MHz)δ: 3.79 (s, 3H), 4.08 (s, 3H), 7.18 (t, J=8.0 Hz, 4H), 7.29 (m, 3H), 7.4(s, 1H), 7.66-7.70 (m, 4H), 7.75-7.80 (m, 4H), 7.94 (d, J=8.0 Hz, 1H),8.26 (d, J=8.0 Hz, 1H), 8.43 (s, 1H), 9.25 (s, 1H).

Example 8 Preparation of Compound

A mixture of the compound of Example 7 (0.1 g, 0.19 mmol) in iodomethane(1 mL) was heated at 60° C. under nitrogen for overnight. The reactionmixture was concentrated to dryness. The residue was treated with Et₂O.A yellow solid was collected to give the desired product (108 mg, 86%).¹H NMR (DMSO, 400 MHz) δ: 3.76 (s, 3H), 4.07 (s, 3H), 4.71 (s, 3H), 7.34(t, J=8.0 Hz, 4H), 7.79 (d, J=8.0 Hz, 4H), 7.88-7.92 (m, 4H), 8.08 (t,J=8.0 Hz, 1H), 8.48 (dd, J=24.0 Hz, 8.0 Hz, 2H), 9.71 (s, 1H), 10.01 (s,1H).

Example 9 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate d in Example 1 (60 mg,0.15 mmol), 4-t-butylphenylboronic acid (46 mg, 0.26 mmol) and potassiumcarbonate (75 mg, 0.54 mmol) in a mixture of acetonitrile (6 mL) andwater (1.5 mL) at room temperature under nitrogen were added palladiumacetate (7.5 mg, 0.03 mmol) and Xphos (30 mg, 0.06 mmol), the resultantmixture was heated at 90° C. for 2 h. It was dried over MgSO₄, filteredand concentrated to a crude product. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-50%) gave the desired product as apale oil (35 mg, 60%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.69 (s, 3H), 4.02 (s,3H), 6.9 (s, 4H), 7.3 (m, 1H), 7.45 (m, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.7(m, 1H), 7.87 (d, J=8.0 Hz, 1H), 8.14 (d, J=8.0 Hz, 1H), 8.29 (s, 1H),9.20 (s, 1H).

Example 10 Preparation of Compound

A mixture of the compound of Example 9 (20 mg, 0.03 mmol) in1-iodopropane (1 mL) was heated at 60° C. under nitrogen for overnight.The reaction mixture was concentrated to dryness. The residue wastreated with Et₂O. A yellow solid was collected to give the desiredproduct (13 mg, 47%). ¹H NMR (DMSO, 400 MHz) δ: 1.03 (t, J=8.0 Hz, 3H),1.35 (s, 9H), 2.06 (qt, 2H), 3.68 (s, 3H), 4.04 (s, 3H), 5.09 (t, J=8.0Hz, 2H), 7.48 (m, 3H), 7.61 (s, 1H), 7.70 (s, 1H), 8.07 (t, J=8.0 Hz,1H), 8.25 (t, J=8.0 Hz, 1H), 8.46 (d, J=8.0 Hz, 1H), 8.64 (d, J=8.0 Hz,1H), 9.70 (s, 1H), 10.00 (s, 1H).

Example 11 Preparation of Compound

A mixture of the compound of Example 9 (10 mg, 0.03 mmol) in iodomethane(0.8 mL) was heated at 60° C. under nitrogen for overnight. The reactionmixture was concentrated to dryness. The residue was treated with Et₂O.A yellow solid was collected to give the desired product (8.0 mg, 59%).¹H NMR (DMSO, 400 MHz) δ: 1.35 (s, 9H), 3.68 (s, 3H), 4.04 (s, 3H), 4.71(s, 3H), 7.51 (s, 4H), 7.61 (s, 1H), 7.70 (s, 1H), 8.08 (t, J=8.0 Hz,1H), 8.26 (t, J=8.0 Hz, 1H), 8.48 (dd, J=16.0 Hz, 2H), 9.68 (s, 1H),9.99 (s, 1H).

Example 12 Preparation of Compound

To a nitrogen-flushed mixture of5-(6,7-dimethoxyquinolin-3-yl)-2,3-dimethoxyphenyltrifluoromethanesulfonate (50 mg, 0.11 mmol), 4-biphenylboronic acid (30mg, 0.15 mmol) and potassium carbonate (35 mg, 0.26 mmol) in a mixtureof dioxane (6 mL) and water (1 mL) at room temperature under nitrogenwere added palladium acetate (5 mg, 0.02 mmol) and Xphos (21 mg, 0.04mmol), the resultant mixture was heated at 95° C. for 3 h. It was driedover MgSO₄, filtered and concentrated to a crude product. Purificationby flash chromatography (SiO₂, EtOAc/hexane 10-50%) gave the desiredproduct SL-1-148 as a pale oil (28 mg, 55%). ¹H NMR (CDCl₃, 400 MHz) δ:3.66 (s, 3H), 3.97 (s, 3H), 4.00 (s, 3H), 4.08 (s, 3H), 7.13 (d, J=16.0Hz, 2H), 7.23 (m, 1H), 7.32 (m, 1H), 7.40 (m, 2H), 7.62 (m, 6H), 7.88(s, 1H), 8.48 (s, 1H), 8.92 (s, 1H).

a. Preparation of Compound

To a solution of 5-(6,7-dimethoxyquinolin-3-yl)-2,3-dimethoxyphenol(0.36 g, 1.1 mmol) and triethylamine (0.30 mL, 2.2 mmol) in CH₂Cl₂ (20mL) at −78° C. under nitrogen was added triflate anhydride (0.26 mL,1.54 mmol) slowly, the resultant mixture was stirred at −78° C. andwarmed up to 0° C. The reaction was diluted with methylenechloride to 50mL and washed with aq. NaHCO₃ solution. The organic solution was driedover MgSO₄ and concentrated to an oil. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-60%) gave the desired product, asan oil (0.28 g, 56%). ¹H NMR (CDCl₃, 400 MHz) δ: 4.00 (s, 3H), 4.04 (s,3H), 4.08 (s, 3H), 4.14 (s, 3H), 5.33 (s, 1H), 7.15 (s, 1H), 7.21 (s,1H), 7.5 (s, 1H), 7.7 (s, 1H), 8.25 (s, 1H), 8.92 (s, 1H).

b. Preparation of Compound

A mixture of 3-(3-(benzyloxy)-,5-dimethoxyphenyl)-67-dimethoxyquinoline(0.58 g, 1.3 mmol), 0.5 mL of HOAc and 10% palladium on carbon (0.12 g,30% w/w) was stirred at room temperature under 1 atm of hydrogenovernight, then at 60° C. for 4 h. The catalyst was filtered off and thefiltrate was concentrated to an oil. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-70%) gave the desired product as awhite solid (0.36 g, 78%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.97 (s, 3H), 3.99(s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 6.00 (s, 1H), 6.75 (s, 1H), 6.95(s, 1H), 7.11 (s, 1H), 7.46 (s, 1H), 8.11 (s, 1H), 8.94 (s, 1H).

c. Preparation of Compound

To a nitrogen-flushed mixture of Intermediate a of Example 1 (0.64 g,2.2 mmol), 3-bromo-6,7-dimethoxyquinoline (0.50 g, 1.9 mmol) andpotassium carbonate (0.77 g, 5.6 mmol) in a mixture of dioxane (20 mL)and water (2 mL) at room temperature under nitrogen was addedtetrakis(triphenylphosphine)palladium (0.11 g, 0.01 mmol), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-50%) to give the desired product as a pale oil (0.57 g, 99%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.97 (s, 3H), 3.99 (s, 3H), 4.05 (s, 3H), 4.06 (s,3H), 5.22 (s, 1H), 6.95 (dd, J=6.0 Hz, 3.0 Hz, 1H), 7.16 (s, 1H),7.2-7.8 (m, 6H), 8.18 (s, 1H), 8.94 (s, 1H).

d. Preparation of Compound

A mixture of 3,4-dimethoxylanline (1.0 g, 6.5 mmol),2-bromomalonaldehyde (1.10 g, 7.28 mmol) and concentrated hydrochloricacid (3.0 mL, 18 mmol) in EtOH (12 mL) was heated at reflux undernitrogen for 12 h. All EtOH and HCl were removed under reduced pressure.The residue was basified with 4 N NaOH to pH 9, extracted with EtOAc(3×30 mL). The EtOAc solution was dried over MgSO₄, filtered andconcentrated and purified with flash column (SiO₂, EtOAc/hexane 0-50%)to give the desired product as a pale oil (0.50 g, 29%). ¹H NMR (CDCl₃,400 MHz) δ: 4.01 (s, 3H), 4.03 (s, 3H), 6.95 (s, 1H), 7.38 (s, 1H), 8.13(s, 1H), 8.71 (s, 1H).

Example 13 Preparation of Compound

The compound of Example 12 (14 mg, 0.03 mmol) in iodomethane (0.5 mL)was heated at 60° C. under nitrogen for overnight. The reaction mixturewas concentrated to dryness. The residue was treated with Et₂O. A yellowsolid was collected to give the desired product (14 mg, 75%). ¹H NMR(DMSO, 400 MHz) δ: 3.69 (s, 3H), 4.04 (s, 6H), 4.17 (s, 3H), 4.64 (s,3H), 7.40 (t, J=8.0 Hz, 1H), 7.51 (m, 2H), 7.59 (s, 1H), 7.67-7.81 (m,9H), 9.45 (s, 1H), 9.68 (s, 1H).

Example 14 Preparation of Compound

The compound of Example 12 (14 mg, 0.03 mmol) in 1-iodopropane (0.5 mL)was heated at 80° C. under nitrogen for 8 h. The reaction mixture wastreated with Et₂O. A yellow solid was collected to give the desiredproduct (12 mg, 64%). ¹H NMR (DMSO, 400 MHz) δ: 1.01 (t, J=8.0 Hz, 3H),2.07 (m, 2H), 3.70 (s, 3H), 4.05 (s, 6H), 4.17 (s, 1H), 5.07 (t, J=8.0Hz, 2H), 7.40 (m, 1H), 7.51 (m, 2H), 7.60 (s, 1H), 7.65-7.80 (m, 6H),7.81 (d, J=8.0 Hz, 3H), 9.46 (s, 1H), 9.67 (s, 1H).

Example 15 Preparation of Compound

To a nitrogen-flushed mixture the Intermediate a of Example 12 (50 mg,0.11 mmol), 4-t-butylphenylboronic acid (30 mg, 0.15 mmol) and potassiumcarbonate (35 mg, 0.26 mmol) in a mixture of dioxane (6 mL) and water (1mL) at room temperature under nitrogen were added palladium acetate (5mg, 0.02 mmol) and Xphos (25 mg, 0.05 mmol), the resultant mixture washeated at 95° C. for 3 h. It was dried over MgSO₄, filtered andconcentrated to a crude product. Purification by flash chromatography(SiO₂, EtOAc/hexane 10-50%) gave the desired product SL-1-148 as a paleoil (29 mg, 60%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.31 (s, 9H), 3.63 (s, 3H),3.96 (s, 3H), 4.00 (s, 3H), 4.09 (s, 3H), 7.08 (s, 1H), 7.40-7.47 (m,6H), 7.9 (s, 1H), 8.52 (s, 1H), 8.91 (s, 1H).

Example 16 Preparation of Compound

The compound of Example 15 (14 mg, 0.03 mmol) in iodomethane (0.5 mL)was heated at 60° C. under nitrogen for 6 h. The reaction mixture wastreated with Et₂O. A yellow solid was collected to give the desiredproduct (6.5 mg, 38%). ¹H NMR (DMSO, 400 MHz) δ: 1.35 (s, 9H), 3.67 (s,3H), 4.03 (s, 3H), 4.17 (s, 3H), 4.63 (s, 3H), 7.53 (m, 5H), 7.64 (m,2H), 7.80 (s, 1H), 9.43 (s, 1H), 9.66 (s, 1H).

Example 17 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate a of Example 12 (50 mg,0.11 mmol), 4-fluorophenylboronic acid (30 mg, 0.21 mmol) and potassiumcarbonate (36 mg, 0.26 mmol) in a mixture of dioxane (8 mL) and water(1.5 mL) at room temperature under nitrogen were added palladium acetate(5 mg, 0.02 mmol) and Xphos (20 mg, 0.04 mmol), the resultant mixturewas heated at 95° C. for 3 h. It was dried over MgSO₄, filtered andconcentrated to a crude product. Purification by flash chromatography(SiO₂, EtOAc/hexane 10-50%) gave the desired product as a pale oil (15mg, 34%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.68 (s, 3H), 4.05 (s, 3H), 4.07(s, 3H), 4.10 (s, 3H), 7.14-7.29 (m, 5H), 7.57-7.64 (m, 3H), 8.25 (s,1H), 9.00 (s, 1H).

Example 18 Preparation of Compound

A mixture of the compound of Example 17 (6.0 mg, 0.01 mmol) iniodomethane (0.5 mL) was heated at 60° C. under nitrogen for 2 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (4.2 mg, 52%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.60(S, 3H), 4.04 (S, 6H), 4.19 (S, 3H), 4.73 (S, 3H), 7.06-7.57 (m, 8H),8.83 (S, 1H), 9.42 (S, 1H).

Example 19 Preparation of Compound

A mixture of the compound of Example 17 (14 mg, 0.03 mmol) in1-iodopropane (0.5 mL) was heated at 80° C. under nitrogen for 8 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (12 mg, 66%). ¹H NMR (DMSO, 400 MHz) δ: 1.00(t, J=8.0 Hz, 3H), 1.35 (s, 9H), 2.06 (qt, 2H), 3.67 (s, 3H), 4.03 (s,6H), 4.17 (s, 3H), 5.65 (t, J=8.0 Hz, 2H), 7.53 (m, 5H), 7.62 (s, 1H),7.68 (s, 1H), 7.81 (s, 1H), 9.44 (s, 1H), 9.65 (s, 1H).

Example 20 Preparation of Compound

To a nitrogen-flushed mixture of the Intermediate a of Example 12 (50mg, 0.11 mmol), 4-cyclohexylphenylboronic acid (45 mg, 0.22 mmol) andpotassium carbonate (50 mg, 0.26 mmol) in a mixture of dioxane (10 mL)and water (2 mL) at room temperature under nitrogen were added palladiumacetate (7.0 mg, 0.03 mmol) and Xphos (30 mg, 0.06 mmol), the resultantmixture was heated at 95° C. for 3 h. It was dried over MgSO₄, filteredand concentrated to a crude product. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-50%) gave the desired product as apale oil (26 mg, 51%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.40-1.90 (m, 10H),2.60 (m, 1H), 3.70 (s, 3H), 4.04 (s, 3H), 4.06 (s, 3H), 4.09 (s, 3H),7.13 (s, 1H), 7.21 (s, 1H), 7.30 (d, J=3.0 Hz, 2H), 7.33 (s, 1H),7.52-7.58 (m, 3H), 8.21 (s, 1H), 9.0 (s, 1H).

Example 21 Preparation of Compound

A mixture of the compound of Example 20 (12 mg, 0.03 mmol) iniodomethane (0.5 mL) was heated at 60° C. under nitrogen for 4 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (12 mg, 77%). ¹H NMR (CDCl₃, 400 MHz) δ:1.47-1.98 (m, 10H), 2.59 (m, 1H), 3.70 (s, 3H), 4.11 (s, 3H), 4.13 (s,3H), 4.86 (s, 3H), 7.31 (m, 5H), 7.60 (d, J=8.0 Hz, 2H), 7.65 (s, 1H),9.06 (s, 1H), 10.11 (s, 1H).

Example 22 Preparation of Compound

A mixture of the compound of Example 20 (12 mg, 0.03 mmol) inisopropyliodide (0.5 mL) was heated at 80° C. under nitrogen for 6 h.The reaction mixture was treated with Et₂O. A yellow solid was collectedto give the desired product (10 mg, 61%). ¹H NMR (CDCl₃, 400 MHz) δ:1.14-1.98 (m, 13H), 2.12 (m, 2H), 2.59 (m, 1H), 3.70 (s, 3H), 4.11 (s,6H), 4.25 (s, 3H), 5.32 (m, 2H), 7.29-7.34 (m, 4H), 7.61 (d, J=8.0 Hz,2H), 7.69 (s, 2H), 9.07 (s, 1H), 9.97 (s, 1H).

Example 23 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate d of Example 26 (50 mg,0.11 mmol), 4-biphenylboronic acid (35 mg, 0.18 mmol) and potassiumcarbonate (45 mg, 0.33 mmol) in a mixture of acetonitrile (9 mL) andwater (1.5 mL) at room temperature under nitrogen were added palladiumacetate (5 mg, 0.02 mmol) and Xphos (20 mg, 0.04 mmol), the resultantmixture was heated at 90° C. for 3 h. It was dried over MgSO₄, filteredand concentrated to a crude product. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-50%) gave the desired productSL-1-148 as a pale oil (20 mg, 40%). ¹H NMR (CDCl₃, 300 MHz) δ: 3.73 (S,3H), 4.06 (S, 3H), 6.16 (S, 2H), 7.14 (S, 1H), 7.23 (S, 1H), 7.32 (d,J=3.0 Hz, 1H), 7.39-7.42 (m, 1H), 7.46-7.52 (m, 3H), 7.69-7.72 (m, 6H),8.16 (S, 1H), 9.00 (S, 1H).

Example 24 Preparation of Compound

A mixture of the compound of Example 23 (11 mg, 0.03 mmol) iniodomethane (0.5 mL) was heated at 60° C. under nitrogen for 2 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (19 mg, 90%). ¹H NMR (DMSO, 400 MHz) δ: 3.69(s, 3H), 4.03 (s, 3H), 4.56 (s, 3H), 6.50 (s, 2H), 7.40-7.82 (m, 12H),8.06 (s, 1H), 9.38 (s, 1H), 9.66 (s, 1H).

Example 25 Preparation of Compound

A mixture of the compound of Example 23 (8.0 mg, 0.02 mmol) inisopropyliodide (0.5 mL) was heated at 80° C. under nitrogen for 6 h.The reaction mixture was treated with Et₂O. A yellow solid was collectedto give the desired product (7 mg, 64%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.82(d, J=8.0 Hz, 6H), 3.63 (S, 3H), 3.96 (S, 3H), 4.35 (m, 1H), 6.06 (S,2H), 6.91 (S, 1H), 7.04 (S, 1H), 7.13-7.62 (m, 11H), 8.05 (S, 1H), 8.90(S, 1H).

Example 26 Preparation of Compound

To a nitrogen-flushed mixture of5-([1,3]dioxolo[4,5-g]quinolin-7-yl)-2,3-dimethoxyphenyltrifluoromethanesulfonate, Intermediate d of Example 26, (50 mg, 0.11mmol), 4-t-butylboronic acid (30 mg, 0.16 mmol) and potassium carbonate(45 mg, 0.33 mmol) in a mixture of acetonitrile (9 mL) and water (1.5mL) at room temperature under nitrogen were added palladium acetate (5mg, 0.02 mmol) and Xphos (20 mg, 0.04 mmol), the resultant mixture washeated at 90° C. for 3 h. It was dried over MgSO₄, filtered andconcentrated to a crude product. Purification by flash chromatography(SiO₂, EtOAc/hexane 10-50%) gave the desired product SL-1-148 as a paleoil (48 mg, 99%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.34 (s, 9H), 3.70 (s, 3H),4.04 (s, 3H), 6.15 (s, 2H), 7.01 (s, 1H), 7.12 (s, 1H), 7.19 (d, J=3.0Hz, 1H), 7.28 (d, J=3.0 Hz, 1H), 7.45-7.59 (m, 4H), 8.14 (s, 1H), 8.98(s, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

Using the same procedure used for Intermediate d in Example 12, the3-bromo-6,7-methylenedioxyquinoline was prepared. A mixture of3,4-methylenedioxylaniline (5.0 g, 36 mmol), 2-bromomalonaldehyde (8.0g, 7.28 mmol) and concentrated hydrochloric acid (18 mL, 216 mmol) inEtOH (35 mL) was heated at reflux under nitrogen for 12 h. All EtOH andHCl were removed under reduced pressure. The residue was basified with 4N NaOH to pH 9, extracted with EtOAc (3×30 mL). The EtOAc solution wasdried over MgSO₄, filtered and concentrated and purified with flashcolumn (SiO₂, EtOAc/hexane 0-50%) to give the desired product as a paleoil (0.45 g, 5%).

b. Preparation of Compound

To a nitrogen-flushed mixture of 3-bromo-6,7-methylenedioxyquinoline(0.64 g, 1.3 mmol), Intermediate a of Example 26 (0.45 g, 1.8 mmol) andpotassium carbonate (0.74 g, 5.4 mmol) in a mixture of dioxane (20 mL)and water (2 mL) at room temperature under nitrogen was addedtetrakis(triphenylphosphine)palladium (0.10 g, 0.09 mmol), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-50%) to give the desired product as a pale oil (0.38 g, 51%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.90 (s, 3H), 3.92 (s, 3H), 5.19 (s, 2H), 6.09 (s,2H), 6.81 (d, J=8.0 Hz, 2H), 7.06 (s, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.35(t, J=8.0 Hz, 2H) 7.42 (m, 3H), 7.9 (s, 1H), 8.80 (s, 1H).

c. Preparation of Compound

A mixture of7-(3-(benzyloxy)-4,5-dimethoxyphenyl)-[1,3-dioxolo[4,5-g]quinoline (0.35g, 0.84 mmol) and 10% palladium on carbon (0.07 g, 20% w/w) was stirredat room temperature under 1 atm of hydrogen at 60° C. for 8 h. Thecatalyst was filtered off and the filtrate was concentrated to give thedesired product (0.27 g, 100%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.72 (s, 3H),3.88 (s, 3H), 6.21 (s, 2H), 6.86 (d, J=12.0 Hz, 2H), 7.35 (d, J=12.0 Hz,2H), 8.33 (s, 1H), 8.91 (s, 1H), 9.32 (s, 1H).

d. Preparation of Compound

To a solution of 5-([13]dioxolo[45-g]quinolin-7-yl)-2,3-dimethoxyphenol(0.27 g, 0.83 mmol) and triethylamine (0.25 mL, 1.8 mmol) in CH₂Cl₂ (25mL) at −(30-40)° C. under nitrogen was added triflate anhydride (0.22mL, 1.3 mmol) slowly, the resultant mixture was stirred at −78° C. andwarmed up to 0° C. The reaction was diluted with methylenechloride to 50mL and washed with aq. NaHCO₃ solution. The organic solution was driedover MgSO₄ and concentrated to an oil. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-60%) gave the desired product asan oil (0.23 g, 60%). ¹H NMR (CDCl₃, 400 MHz) δ: 4.02 (s, 3H), 4.03 (s,3H), 6.17 (s, 2H), 7.12 (m, 2H), 7.18 (d, J=3.0 Hz, 1H), 7.44 (s, 1H),8.07 (s, 1H), 8.89 (s, 1H).

Example 26a Preparation of Compound

A mixture of the compound of Example 26 (11 mg, 0.03 mmol) iniodomethane (0.5 mL) was heated at 60° C. under nitrogen for overnight.The reaction mixture was concentrated to dryness. The residue wastreated with Et₂O. A yellow solid was collected to give the desiredproduct (13 mg, 89%). ¹H NMR (CDCl₃, 300 MHz) δ: 1.38 (S, 9H), 3.72 (S,3H), 4.21 (S, 3H), 4.80 (S, 3H), 6.38 (S, 2H), 7.27 (m, 3H), 7.42 (S,1H), 7.51 (d, J=9.0 Hz, 1H), 7.63 (m, 2H), 7.77 (S, 1H), 9.00 (S, 1H),10.09 (S, 1H).

Example 27 Preparation of Compound

To a nitrogen-flushed mixture of Intermediate d of Example 29 (30 mg,0.06 mmol), 3-t-butylphenylboronic acid (20 mg, 0.11 mmol) and potassiumcarbonate (26 mg, 0.19 mmol) in a mixture of acetonitrile (6 mL) andwater (1 mL) at room temperature under nitrogen were added palladiumacetate (5 mg, 0.02 mmol) and Xphos (20 mg, 0.04 mmol), the resultantmixture was heated at 90° C. for 4 h. It was dried over MgSO₄, filteredand concentrated to a crude product. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-50%) gave the desired productSL-1-148 as a pale oil (19 mg, 66%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.40 (s,9H), 3.69 (s, 3H), 4.05 (s, 3H), 4.08 (s, 3H), 4.19 (s, 3H), 7.24 (d,J=3.0 Hz, 1H), 7.31 (d, J=3.0 Hz, 1H), 7.41-7.44 (m, 4H), 7.65 (d, J=9.0Hz, 1H), 7.71 (m, 1H), 8.26 (s, 1H), 9.24 (s, 1H).

Example 28 Preparation of Compound

A mixture of the compound of Example 27 (18 mg, 0.04 mmol) iniodomethane (0.3 mL) was heated at 80° C. under nitrogen for 1 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (11 mg, 47%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.37(S, 9H), 3.47 (S, 3H), 3.87 (S, 3H), 3.95 (S, 3H), 4.02 (S, 3H), 4.92(S, 3H), 6.99 (S, 1H), 7.17-7.21 (m, 3H), 7.44-7.47 (m, 2H), 7.77 (d,J=4.0 Hz, 1H), 7.84 (d, J=8.0 Hz, 1H), 8.72 (S, 1H), 9.81 (S, 1H).

Example 29 Preparation of Compound

To a nitrogen-flushed mixture of5-(7,8-dimethoxyquinolin-3-yl)-2,3-dimethoxyphenyl trifluoromethanesulfonate (75 mg, 0.16 mmol), 4-t-butylphenylboronic acid (45 mg, 0.25mmol) and potassium carbonate (60 mg, 0.43 mmol) in a mixture ofacetonitrile (9 mL) and water (2 mL) at room temperature under nitrogenwere added palladium acetate (7 mg, 0.03 mmol) and Xphos (30 mg, 0.06mmol), the resultant mixture was heated at 90° C. for 3 h. It was driedover MgSO₄, filtered and concentrated to a crude product. Purificationby flash chromatography (SiO₂, EtOAc/hexane 10-50%) gave the desiredproduct SL-1-148 as a pale oil (45 mg, 61%). ¹H NMR (CDCl₃, 400 MHz) δ:1.40 (s, 9H), 3.70 (s, 3H), 4.04 (s, 3H), 4.07 (s, 3H), 4.19 (s, 3H),7.23 (d, J=3.0 Hz, 1H), 7.31 (d, J=3.0 Hz, 1H), 7.42 (d, J=9.0 Hz, 1H),7.50 (m, 2H), 7.57-7.65 (m, 3H), 8.25 (d, J=3.0 Hz, 1H), 9.23 (d, J=3.0Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A mixture of 2,3-dimethoxylaniline (2.0 g, 13 mmol),2-bromomalonaldehyde (2.5 g, 17 mmol) and concentrated hydrochloric acid(8 mL, 96 mmol) in EtOH (35 mL) was heated at reflux under nitrogen for16 h. All EtOH and HCl were removed under reduced pressure. The residuewas basified with 4 N NaOH to pH 9, extracted with EtOAc (3×30 mL). TheEtOAc solution was dried over MgSO₄, filtered and concentrated andpurified with flash column (SiO₂, EtOAc/hexane 0-50%) to give thedesired product as a pale oil (0.31 g, 38%). ¹H NMR (CDCl₃, 400 MHz) δ:4.06 (s, 3H), 4.14 (s, 3H), 7.40 (d, J=6.0 Hz, 1H), 7.53 (d, J=6.0 Hz,1H), 8.26 (s, 1H), 8.91 (s, 1H).

b. Preparation of Compound

To a nitrogen-flushed mixture of the Intermediate a of Example 1 (0.40g, 1.4 mmol), 3-bromo-7,8-dimethoxyquinoline (0.30 g, 1.1 mmol) andpotassium carbonate (0.45 g, 3.3 mmol) in a mixture of dioxane (10 mL)and water (2 mL) at room temperature under nitrogen was addedtetrakis(triphenylphosphine)palladium (65 mg, 0.06 mmol), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-60%) to give the desired product as a pale oil (0.25 g, 52%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.97 (s, 3H), 3.99 (s, 3H), 4.08 (s, 3H), 4.19 (s,3H), 5.26 (s, 2H), 6.91 (d, J=16.0 Hz, 2H), 7.35 (d, J=4.0 Hz, 1H), 7.42(m, 3H), 7.50 (d, J=8.0 Hz, 1H), 8.16 (s, 1H), 9.11 (s, 1H).

c. Preparation of Compound

A mixture of 3-(3-benzyloxy)-4,5-dimethoxyphenylquinoline (0.25 g, 0.58mmol) and 10% palladium on carbon (40 mg, 16% w/w) was stirred under 1atm of hydrogen at 60° C. for 6 h. The catalyst was filtered off and thefiltrate was concentrated to to an oil. Purification by flashchromatography (SiO₂, EtOAc/hexane 10-60%) gave the desired product(0.20 g, 100%). ¹H NMR (CD₃OD, 300 MHz) δ: 3.88 (S, 3H), 4.00 (S, 3H),4.20 (S, 6H), 7.00-7.02 (m, 2H), 7.93 (d, J=9.0 Hz, 1H), 8.15 (d, J=9.0Hz, 1H), 9.23 (dd, J=9.0 Hz, 3.0 Hz, 2H).

d. Preparation of Compound

To a solution of 5-(7,8-dimethoxyquinolin-3-yl)-2,3-dimethoxyphenol(0.21 g, 0.61 mmol) and triethylamine (0.17 mL, 1.2 mmol) in CH₂Cl₂ (25mL) at −30° C. under nitrogen was added triflate anhydride (0.26 mL, 1.5mmol) slowly, the resultant mixture was stirred at −30° C. and warmed upto 0° C. The reaction was diluted with methylenechloride to 50 mL andwashed with aq. NaHCO₃ solution. The organic solution was dried overMgSO₄ and concentrated to an oil. Purification by flash chromatography(SiO₂, EtOAc/hexane 10-60%) gave the desired product as an oil (0.15 g,51%). ¹H NMR (CDCl₃, 300 MHz) δ: 4.03 (S, 3H), 4.04 (S, 3H), 4.09 (S,3H), 4.18 (S, 3H), 7.14 (d, J=3.0 Hz, 1H), 7.21 (d, J=3.0 Hz, 1H), 7.45(d, J=9.0 Hz, 1H), 7.68 (d, J=9.0 Hz, 1H), 8.19 (d, J=3.0 Hz, 1H), 9.13(S, 1H).

Example 30 Preparation of Compound

A mixture of the Compound of Example 29 (12 mg, 0.03 mmol) iniodomethane (0.5 mL) was heated at 80° C. under nitrogen for 2 h. Thereaction mixture was treated with Et₂O. A yellow solid was collected togive the desired product (7.4 mg, 47%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.30(s, 9H), 3.62 (s, 3H), 3.98 (s, 3H), 4.07 (s, 3H), 4.11 (s, 3H), 5.01(s, 3H), 7.16 (s, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.49 (d, J=8.0 Hz, 2H),7.56 (d, J=8.0 Hz, 1H), 7.81 (d, J=4.0 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H),8.95 (s, 1H), 9.88 (s, 1H).

Example 31 Preparation of Compound

A mixture oft-butyl((3-(4′-(tert-butyl)-5,6-dimethoxy-[1,1′-biphenyl]-3-yl)quinolin-2-yl)methyl)carbamate(8.8 mg, 0.02 mmol) in a mixture of TFA/CH₂Cl₂ (0.1/0.1 mL) was set atroom temperature overnight. All TFA/CH₂Cl₂ were removed under reducedpressure to give the desired product as a pale oil (9 mg, 100%). ¹H NMR(CDCl₃, 400 MHz) δ: 3.69 (s, 3H), 3.90 (s, 3H0, 4.48 (s, 2H), 7.06 (d,J=3.0 Hz, 1H), 7.15 (d, J=3.0 Hz, 1H), 7.48-7.56 (m, 3H), 7.69 (t, J=6.0Hz, 2H), 7.85 (t, J=6.0 Hz, 2H), 8.04 (d, J=6.0 Hz, 1H), 8.19 (d, J=6.0Hz, 1H), 8.35 (s, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a nitrogen-flushed mixture of intermediate a of Example 1 (0.38 g,1.3 mmol), 3-bromo-2-formylquinoline (0.26 g, 1.1 mmol) (Eur. J. Org.Chem. 1781, 2009) and potassium carbonate (0.45 g, 3.3 mmol) in amixture of dioxane (10 mL) and water (2 mL) at room temperature undernitrogen was added tetrakis(triphenylphosphine)palladium (60 mg, 0.05mmol), the resultant mixture was heated at 100° C. for 3.5 h. It wasdried over MgSO₄, filtered and concentrated and purified with flashcolumn (SiO₂, EtOAc/hexane 10-60%) to give the desired product as a paleoil (0.44 g, 100%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.92 (s, 3H), 3.99 (s,3H), 5.2 (s, 2H), 6.68 (d, J=6.0 Hz, 2H), 7.34-7.49 (m, 5H), 7.70-7.76(m, 1H), 7.83-7.93 (m, 2H), 8.20 (s, 1H), 8.36 (d, J=9.0 Hz, 1H), 10.24(s, 1H).

b. Preparation of Compound

A mixture of3-(3-(benzyloxy)-4,5-dimethoxyphenyl)quinoline-2-carboxaldehyde (0.15 g,0.37 mmol) and 10% palladium on carbon (15 mg, 10% w/w) in MeOH (20 mL)was stirred under 1 atm of hydrogen at r.t for 6 h. The catalyst wasfiltered off and the filtrate was concentrated to to an oil.Purification by flash chromatography (SiO₂, EtOAc/hexane 10-60%) gavethe desired product (34 mg, 23%). ¹H NMR (CDCl₃, 400 MHz) δ: 3.88 (s,3H), 3.98 (s, 3H), 4.82 (s, 2H), 5.14 (bs, 1H), 6.06 (bs, 1H), 6.46 (d,J=3.0 Hz, 1H), 6.61 (d, J=3.0 Hz, 1H), 7.56 (dt, J=6.0 Hz, 3.0 Hz, 1H),7.71-7.70 (m, 1H), 7.84 (d, J=9.0 Hz, 1H), 8.01 (s, 1H), 8.12 (d, J=9.0Hz, 1H).

c. Preparation of Compound

To a mixture of(3-(3-(benzyloxy)-4,5-dimethoxyphenyl)quinolin-2-yl)methanol (64 mg,0.16 mmol) in THF (5 mL) at 0° C. under nitrogen were added DPPA (0.07mL, 0.32 mmol) and then DBU (0.05 mL, 0.33 mmol) dropwise, the resultantmixture was stirred at 0° C. and warwed up to r.t overnight. Thereaction mixture was diluted with EtOAc to 30 mL, washed with aq NaHCO₃solution and brine. It was dried over MgSO₄, filtered and concentratedand purified with flash column (SiO₂, EtOAc/hexane 10-60%) to give thedesired product as a pale oil (42 mg, 62%). ¹H NMR (CDCl₃, 400 MHz) δ:3.93 (s, 3H), 3.99 (s, 3H), 4.52 (s, 3H), 5.22 (s, 2H), 6.69 (s, 2H),6.68 (s, 2H), 7.35-7.48 (m, 3H), 7.65 (t, J=6.0 Hz, 1H), 7.8 (m, 1H),7.87 (d, J=9.0 Hz, 1H), 8.14 (s, 1H), 8.25 (d, J=6.0 Hz, 1H).

d. Preparation of Compound

A mixture of2-(azidomethyl)-3-(3-(benzyloxy)-4,5-dimethoxyphenyl)quinoline (83 mg,0.19 mmol), Boc anhydride (80 mg, 0.37 mmol) and 10% palladium on carbon(16 mg, 20% w/w) in MeOH (20 mL) was stirred under 1 atm of hydrogen atr.t overnight. The catalyst was filtered off and the filtrate wasconcentrated to to an oil. Purification by flash chromatography (SiO₂,EtOAc/hexane 10-60%) gave the desired product (15 mg, 19%). ¹H NMR(CDCl₃, 400 MHz) δ: 1.52 (s, 9H), 3.90 (s, 3H), 3.99 (s, 3H), 4.57 (d,J=3.0 Hz, 2H), 5.96 (bs, 1H), 6.46 (d, J=3.0 Hz, 1H), 6.55 (bs, 1H),6.62 (d, J=3.0 Hz, 1H), 7.55-7.60 (m, 1H), 7.72-7.78 (m, 1H), 7.84 (d,J=9.0 Hz, 1H), 8.00 (s, 1H), 8.15 (d, J=9.0 Hz, 1H).

e. Preparation of Compound

To a solution oft-butyl((3-(3-hydroxy-4,5-dimethoxyphenyl)quinolin-2-yl)methylcarbamate(13 mg, 0.03 mmol) and triethylamine (0.009 mL, 0.06 mmol) in CH₂Cl₂ (2mL) at −78° C. under nitrogen was added triflate anhydride (0.008 mL,0.05 mmol) slowly, the resultant mixture was stirred at −78° C. for 20min and warmed up to −10° C. The reaction was diluted withmethylenechloride to 50 mL and washed with aq. NaHCO₃ solution. Theorganic solution was dried over MgSO₄ and concentrated to an oil.Purification by flash chromatography (SiO₂, EtOAc/hexane 10-60%) gavethe desired product as an oil (15 mg, 88%). ¹H NMR (CDCl₃, 400 MHz) δ:1.52 (s, 9H), 3.96 (s, 3H), 4.06 (s, 3H), 4.53 (d, J=3.0 Hz, 2H), 6.47(bs), 6.89 (s, 1H), 6.96 (s, 1H), 7.61 (t, J=6.0 Hz, 1H), 7.66-7.82 (m,1H), 7.86 (d, J=6.0 Hz, 1H), 8.03 (s, 1H), 8.16 (d, J=9.0 Hz, 1H).

f. Preparation of Compound

A mixture of5-(2-(((t-butoxycarbonyl)amino)methyl)quinolin-3-yl)-2,3-dimethoxyphenyltrifluoromethanesulfonate (15 mg, 0.028 mmol), t-butylphenylboronic acid(7 mg), Pd (OAc)₂ (2 mg), XPhos (4 mg), K₂CO₃ (10 mg) in ACN: H₂O (3.0ml:0.3 ml) was heated at 90° C. for 5 h. The reaction mixture was driedand chromatographed to yield 8.8 mg (59%) product. ¹H NMR (CDCl₃, 400MHz) δ: 1.34 (s, 9H), 1.52 (s, 9H), 3.72 (s, 3H), 3.96 (s, 3H), 4.62 (d,J=3.0 Hz, 2H), 6.58 (bs, 1H), 6.9 (d, J=18.0 Hz, 2H), 7.47 (m, 2H),7.56-7.61 (m, 3H), 7.76 (t, J=6.0 Hz, 1H).

Example 32 Preparation of Compound

A mixture of 4-biphenylboronic acid (0.2 g), 2,3-difluorophenyltriflate(0.1 g), Cs₂CO₃ (0.4 g), Pd (PPh₃)₂Cl₂ (5 mol %) in dioxane (3.0 mL) wasmicro waved for 15 minutes. The crude reaction mixture was diluted withethyl acetate and was filtered through a plug of Celite and silica gel.The filtrate was concentrated under vacuo and was subjected to flashcolumn chromatography to afford the desired product (0.115 g). ¹H NMR(CDCl₃, 400 MHz) δ: 7.34 (m, 1H), 7.39-7.50 (m, 3H), 7.51-7.5 (m, 2H),7.58 (m, 2H), 7.64 (m, 5H), 7.83 (d, J=8.0 Hz, 1H), 8.09 (d, J=8.0 Hz,1H), 8.25 (d, J=4.0 Hz, 1H), 9.10 (s, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A mixture of quinoline 3-boronic acid (0.34 g, 2.0 mmol),5-bromo-2,3-difluorophenol (0.5 g, 2.5 mmol), Cs₂CO₃ (0.8 g), Pd(PPh₃)₂Cl₂ (5 mol %) in dioxane (3.0 mL) was micro waved for 15 minutes.The crude reaction mixture was diluted with ethyl acetate and wasfiltered through a plug of Celite and silica gel. The filtrate wasconcentrated under vacuo and was subjected to flash columnchromatography to afford the desired product (0.35 g). ¹H NMR (CDCl₃,400 MHz) δ: 7.09-7.13 (m, 1H), 7.24-7.26 (m, 1H), 7.65 (m, 1H), 7.80 (m,1H), 7.93 (d, J=8.0 Hz, 1H), 8.22 (d, J=8.0 Hz, 1H), 8.32 (s, 1H), 9.22(s, 1H).

b. Preparation of Compound

The hydroxyl compound (120 mg) was dissolved in dichloromethane (3.0 mL)to which added 2.0 equivalent of triethyl amine and 1.5 equivalent ofTf₂O at −78° C. After the reaction is completed, the reaction mixturewas diluted with more methylene chloride which was then washed withsaturated sodium bicarbonate and brine. The crude mixture was thenpurified by flash column chromatography to afford the product (110 mg).¹H NMR (CDCl₃, 400 MHz) δ: 7.32 (m, 1H), 7.42-7.52 (m, 2H), 7.63-7.68(m, 1H), 7.78 (d, J=8.0 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 8.13 (s, 1H),8.94 (d, J=4.0 Hz, 1H).

Example 33 Preparation of Compound

The starting material (50 mg) was dissolved in methyl iodide (2.0 ml) ina sealed tube and was heated at 80° C. for 30 minutes. The resultingsolid was then diluted with acetone, filtered and washed with diethylether twice to afford the quaternary salts as pure solid (40 mg). ¹H NMR(CDCl₃, 400 MHz) δ: 7.36 (m, 2H), 7.61 (m, 2H), 7.76 (m, 2H), 7.90 (m,3H), 8.0-8.3 (m, 6H), 9.04 (s, 1H), 10.1 (s, 1H).

Example 34 Preparation of Compound

To a nitrogen-flushed mixture of 3-bromoquinoline (1 equiv),terphenylboronic acid (1.5 equiv), and Potassium carbonate in a mixtureof acetonitrile and water at room temperature were added palladiumacetate (5 mol %) and Xphos (10 mol %). The resultant mixture was heatedat 90° C. for 3 h. It was dried over MgSO4, filtered and concentrated toa crude product. Purification on silica using 10% EtOAc in hexaneafforded the pure product. ¹H NMR (CDCl₃, 400 MHz) δ: 7.43-7.47 (m, 2H),7.54 (m, 4H), 7.65 (m, 1H), 7.77 (m, 5H), 7.90-7.95 (m, 4H), 8.22 (d,J=12.0 Hz, 1H), 8.44 (s, 1H), 9.33 (s, 1H).

Example 35 Preparation of Compound

The compound of Example 34 (150 mg) was dissolved in methyl iodide (2ml) in a sealed tube and was heated at 80° C. for 15 minutes. Theresulting solid was then diluted with acetone, filtered and washed withdiethyl ether twice to afford the quaternary salts as pure solid (110mg). ¹H NMR (CDCl₃, 400 MHz) δ: 7.31 (m, 2H), 7.41 (m, 4H), 7.75 (m,4H), 7.81 (s, 1H), 7.85 (t, J=8.0 Hz, 1H), 8.03 (s, 2H), 8.08 (t, J=8.0Hz, 1H), 8.2 (d, J=8.0 Hz, 1H), 8.34 (d, J=8.0 Hz, 1H), 9.20 (s, 1H),10.12 (s, 1H).

Example 36 Preparation of Compound

A solution of 2-(5-(4-t-butyl)phenyl)naphthalen-1-yl)acetonitrile (85mg, 0.28 mmol) in THF (5 mL) was added dropwise to a solution of LiAlH₄(1.0 M/THF, 0.9 mL) in THF (5 mL) at 0° C. under nitrogen, the resultantmixture was heated at reflux for 7 h. It was cooled to 0° C. andcarefully treated with aq NaOH and extracted with EtOAc (3×20 mL) anddried over MgSO₄, filtered and concentrated. Purification with flashcolumn (SiO₂, 1.5% NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product asa pale oil (15 mg, 17%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.34 (s, 3H), 1.92(bs, 2H), 3.08 (t, J=6.0 Hz, 1H), 3.21 (t, J=6.0 Hz, 1H), 7.29 (m, 2H),3.34 (m, 3H), 7.41-7.5 (m, 3H), 7.77 (d, J=6.0 Hz, 1H), 8.99 (d, J=6.0Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a solution of (5-(4-(t-butyl)phenyl)naphthalen-1-yl)methanol (1.0 g,3.4 mmol) and triethylamine (0.80 mL, 5.8 mmol) in CH₂Cl₂ (25 mL) at 0°C. under nitrogen was added methanesulfonyl chloride (0.33 mL, 4.3 mmol)slowly, the resultant mixture was stirred at 0° C. for 30 min. Thereaction was quenched with aq. NaHCO₃ solution and extracted with EtOAc(3×30 mL). The organic solution was dried over MgSO₄ and concentrated toan oil.

A mixture of the oil residue prepared above and KCN (0.31 g, 4.8 mmol)in DMSO (10 mL) was stirred at room temperature overnight. Water wasadded, the reaction mixture was extracted with EtOAc (3×80 mL). TheEtOAc solution was washed with water and brine, dried over over MgSO₄,filtered and concentrated. Purification with flash column (SiO₂,EtOAc/hexane 10-50%) gave the desired product as a pale oil (0.51 g,50%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.46 (s, 9H), 4.24 (s, 2H).

b. Preparation of Compound

A mixture of 5-(4-(t-butyl)phenyl)-1-naphthaldehyde (0.75 g, 2.6 mmol)and NaBH₄ (70 mg, 1.85 mmol) in 95% EtOH (20 mL) was stirred at roomtemperature for 1 h. It was filtered and the filtrate was concentratedand redissolved in EtOAc (80 mL). The EtOAc solution was washed with aq.NaHCO₃ and brine, dried over over MgSO₄, filtered and concentrated.Purification with flash column (SiO₂, EtOAc/hexane 10-30%) gave thedesired product as a white solid (0.74 g, 99%). ¹H NMR (CDCl₃, 300 MHz)δ: 1.41 (S, 9H), 5.20 (d, J=3.0 Hz, 2H), 7.36-7.62 (m, 8H), 7.94 (d,J=9.0 Hz, 1H), 8.16 (d, J=9.0 Hz, 1H).

c. Preparation of Compound

To a nitrogen-flushed mixture of 5-bromo-1-naphthaldehyde (0.50 g, 2.1mmol) (J. Med. Chem., 36, 2810, 1993), 4-t-butylphenylboronic acid (0.47g, 2.6 mmol) and potassium carbonate (0.88 g, 6.4 mmol) in a mixture ofdioxane (15 mL) and water (3 mL) at room temperature under nitrogen wasadded tetrakis(triphenylphosphine)-palladium (73 mg, 0.06 mmol), theresultant mixture was heated at 100° C. for 5 h. It was dried overMgSO₄, filtered and concentrated and purified with flash column (SiO₂,EtOAc/hexane 10-50%) to give the desired product as a pale solid (0.49g, 88%). ¹H NMR (CDCl₃, 300 MHz) δ: 1.42 (S, 9H), 7.39-7.42 (m, 2H),7.51-7.60 (m, 4H), 7.70-7.76 (m, 1H), 8.00 (d, J=9.0 Hz, 1H), 8.24 (d,J=9.0 Hz, 1H), 9.29 (d, J=6.0 Hz, 1H), 10.45 (S, 1H).

Example 37 Preparation of Compound

The Intermediate a for Example 37 (40 mg, 0.09 mmol) in a mixture ofTFA/CH₂Cl₂ (0.8/0.8 mL) was set at room temperature overnight. AllTFA/CH₂Cl₂ were removed under reduced pressure, the residue was purifiedwith flash column (SiO₂, 3% NH4OH-MeOH/CH₂Cl₂ 0-15%) gave the desiredproduct as a white solid (29 mg, 96%). ¹H NMR (CD₃OD, 300 MHz) δ: 1.43(S, 9H), 3.46 (t, J=6.0 Hz, 2H), 3.66 (t, J=6.0 Hz, 2H), 7.36-7.45 (m,5H), 7.55-7.65 (m, 3H), 7.81 (d, J=9.0 Hz, 1H), 8.13 (d, J=9.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

The compound of Example 36 (35 mg, 0.12 mmol) and triethylamine (0.04mL, 0.29 mmol) in CH₂Cl₂ (6 mL) was added di-Boc guanidine triflate (55mg, 0.14 mmol). The reaction mixture was stirred at room temperatureovernight. The reaction mixture was concentrated to an oily residue.Purification with flash column (SiO₂, EtOAc/hexane 10-20%) gave thedesired product as a white solid (51 mg, 81%). ¹H NMR (CDCl₃, 300 MHz)δ: 1.41 (S, 9H), 1.43 (S, 9H), 1.56 (S, 9H), 3.43 (t, J=6.0 Hz, 2H), 3.8(m, 2H), 7.33-7.46 (m, 4H), 7.50-7.62 (m, 3H), 7.87 (dd, J=6.0 Hz, 3.0Hz, 1H), 8.30 (d, J=9.0 Hz, 1H), 8.50 (t, J=3.0 Hz, 1H).

Example 38 Preparation of Compound

A solution of Intermediate c of Example 38 (0.30 g, 0.90 mmol) in THF (5mL) was added dropwise to a solution of LiAlH₄ (1.0 M/THF, 2.7 mL) inTHF (5 mL) at 0° C. under nitrogen, the resultant mixture was stirred atroom temperature overnight. It was cooled to 0° C. and carefully treatedwith aq NaOH and extracted with EtOAc (3×20 mL) and dried over MgSO₄,filtered and concentrated. Purification with flash column (SiO₂, 3%NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product as a white solid (75mg, 27%). ¹H NMR (CD₃OD, 300 MHz) δ: 1.40 (S, 9H), 3.08 (t, J=6.0 Hz,2H), 3.33 (m, 2H), 7.29-7.43 (m, 5H), 7.49-7.57 (m, 3H), 7.89 (d, J=6.0Hz, 1H), 8.17 (d, J=6.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a solution of 4-hydroxynaphalenaldehyde (0.50 g, 2.8 mmol) andtriethylamine (0.78 mL, 5.6 mmol) in CH₂Cl₂ (10 mL) at −62° C. undernitrogen was added triflate anhydride (0.70 mL, 4.2 mmol) slowly, theresultant mixture was stirred at −60° C. for 30 min. The reaction wasquenched with aq. NaHCO₃ solution and extracted with methylenechloride(3×30 mL). The organic solution was dried over MgSO₄ and concentrated toan oil. Purification by flash chromatography (SiO₂, EtOAc/hexane 10-60%)gave the desired product as a pale solid (0.56 g, 66%). ¹H NMR (CDCl₃,300 MHz) δ: 7.65 (d, J=9.0 Hz, 1H), 7.74-7.85 (m, 2H), 8.05 (d, J=6.0Hz, 1H), 8.18 (d, J=9.0 Hz, 1H), 9.32 (d, J=9.0 Hz, 1H), 10.42 (S, 1H).

b. Preparation of Compound

To a nitrogen-flushed mixture of 4-formylnaphthalen-1-yltrifluoromethanesulfonate (0.56 g, 1.8 mmol), 4-t-butylphenylboronicacid (0.60 g, 3.3 mmol) and potassium carbonate (0.85 g, 6.2 mmol) in amixture of acetonitrile (10 mL) and water (2 mL) at room temperatureunder nitrogen were added palladium acetate (30 mg, 0.13 mmol) and Xphos(120 mg, 0.25 mmol), the resultant mixture was heated at 90° C. for 6 h.It was dried over MgSO₄, filtered and concentrated to a crude product.Purification by flash chromatography (SiO₂, EtOAc/hexane 10-50%) gavethe desired product as a pale solid (0.52 g, 99%). ¹H NMR (CDCl₃, 300MHz) δ: 1.43 (S, 9H), 7.41-7.49 (m, 6H), 7.54 (m, 1H), 7.74 (d, J=9.0Hz, 1H), 8.01 (d, J=9.0 Hz, 1H), 8.16 (d, J=9.0 Hz, 1H), 10.46 (S, 1H).

c. Preparation of Compound

A mixture of 4-(4-t-butylphenyl)-1-naphthaldehyde (0.26 g, 0.9 mmol) andammonium acetate (80 mg, 1.0 mmol) in nitromethane (3 mL) was heated atreflux for 2 h. The reaction mixture was concentrated to an oil residue.Purification with flash column (SiO₂, EtOAc/hexane 5-30%) gave thedesired product as a pale oil (0.30 g, 100%). ¹H NMR (CDCl₃, 300 MHz) δ:1.43 (S, 9H), 7.39-7.56 (m, 6H), 7.66-7.73 (m, 2H), 7.81 (dd, J=9.0 Hz,3.0 Hz, 1H), 8.05 (d, J=6.0 Hz, 1H), 8.21 (d, J=6.0 Hz, 1H), 8.91 (dd,J=9.0 Hz, 3.0 Hz, 1H).

Example 39 Preparation of Compound

A mixture of Intermediate a of Example 39 (36 mg, 0.07 mmol) in amixture of TFA/CH₂Cl₂ (0.8/0.8 mL) was set at room temperatureovernight. All TFA/CH₂Cl₂ were removed under reduced pressure, theresidue was purified with flash column (SiO₂, 3% NH₄OH-MeOH/CH₂Cl₂0-20%) gave the desired product to give the desired product as a whitesolid (21 mg, 91%). ¹H NMR (CD₃OD, 300 MHz) δ: 1.43 (S, 9H), 3.44 (t,J=6.0 Hz, 2H), 3.66 (t, J=6.0 Hz, 2H), 7.38 (m, 3H), 7.47 (m, 2H), 7.57(m, 3H), 7.92 (d, J=6.0 Hz, 1H), 8.16 (d, J=6.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

The compound of Example 382-(4-(4-(t-butyl)phenyl)naphthalen-1-yl)ethanamine, (25 mg, 0.08 mmol)and triethylamine (0.03 mL, 0.22 mmol) in CH₂Cl₂ (4 mL) was added di-Bocguanidine triflate (40 mg, 0.10 mmol). The reaction mixture was stirredat room temperature overnight. The reaction mixture was concentrated toan oil residue. Purification with flash column (SiO₂, EtOAc/hexane5-10%) gave the desired product as a white solid (38 mg, 84%). ¹H NMR(CDCl₃, 300 MHz) δ: 1.42 (S, 9H), 1.49 (S, 9H), 1.55 (S, 9H), 3.42 (t,J=6.0 Hz, 2H), 3.82 (m, 2H), 7.34-7.56 (m, 7H), 8.18 (d, J=6.0 Hz, 1H),8.35 (d, J=9.0 Hz, 1H), 8.50 (m, 1H).

Example 40 Preparation of Compound

A mixture of Intermediate b of Example 40 (70 mg, 0.13 mmol) in amixture of TFA/CH₂Cl₂ (0.5/0.5 mL) was set at room temperatureovernight. All TFA/CH₂Cl₂ were removed under reduced pressure, theresidue was purified with flash column (SiO₂, 3% NH₄OH-MeOH/CH₂Cl₂0-20%) gave the desired product to give the desired product as a whitesolid (35 mg, 80%). ¹H NMR (CDCl₃, 300 MHz) δ: 1.41 (S, 9H), 7.39 (m,2H), 7.47 (d, J=9.0 Hz, 1H), 7.52 (d, J=9.0 Hz, 1H), 7.60 (m, 4H), 7.90(d, 1H), 7.98 (d, J=9.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A mixture of 4-(4-tert-butylphenyl)-1-naphthaldehyde (0.26 g, 0.90 mmol)and NaBH₄ (70 mg, 1.85 mmol) in 95% EtOH (10 mL) was stirred at roomtemperature for 2 h. It was filtered and the filtrate was concentratedand redissolved in CH₂Cl₂ (40 mL). The CH₂Cl₂ solution was washed withaq. NaHCO₃ and brine, dried over over MgSO₄, filtered and concentrated.Purification with flash column (SiO₂, EtOAc/hexane 10-30%) gave thedesired product as a white solid (0.16 g, 63%). ¹H NMR (CDCl₃, 300 MHz)δ: 1.42 (S, 9H), 1.76 (t, 1H), 5.21 (d, J=6.0 Hz, 2H), 7.40-7.59 (m,8H), 8.0 (d, J=6.0 Hz, 1H), 8.20 (d, J=6.0 Hz, 1H).

b. Preparation of Compound

To a mixture of 4-(4.(t-butyl)phenyl)naphthalen-1-yl)methanol (40 mg,0.14 mmol), di-Boc guanidine (70 mg, 0.27 mmol) and Ph₃P (60 mg, 0.23mmol) in toluene (3 mL) at 0° C. under nitrogen was added DIAD (0.04 mL,0.20 mmol). The reaction mixture was stirred at room temperatureovernight. The reaction mixture was concentrated to an oil residue.Purification with flash column (SiO₂, EtOAc/hexane 0-30%) gave thedesired product as a yellow solid (70 mg, 97%). ¹H NMR (CDCl₃, 300 MHz)δ: 1.44 (S, 9H), 1.45 (S, 9H), 1.48 (S, 9H), 5.78 (S, 2H), 7.23 (d,J=6.0 Hz, 1H), 7.30-7.52 (m, 7H), 8.06 (m, 2H), 9.51 (bs, 2H).

Example 41 Preparation of Compound

To a solution of crude 1-(azidomethyl)-5-(4-t-butyl)phenyl)naphthalene(50 mg) in 5.0 ml of THF and 0.5 ml of water was added 300 mg of thepolymer supported PPh₃. The reaction mixture was stirred at roomtemperature overnight after which the solids were filtered off andpurified by column chromatography to furnish the desired amine. ¹H NMR(CDCl₃, 400 MHz) δ: 1.34 (s, 9H), 1.58 (bs, 2H), 4.31 (s, 2H), 7.29-7.44(m, 7H), 7.51 (m, 1H), 7.80 (d, J=8.0 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a mixture of the alcohol (66 mg, 0.23 mmol) in 1:4 (CCl₄:DMF) wasadded sodium azide (18 mg, 0.27 mmol) and PPh₃ (125 mg, 0.48 mmol). Thereaction mixture was heated at 90° C. overnight. Removal of the solventand chromatography yielded azido compound partially mixed with PPh₃. Thecrude mixture was not purified and was used directly to form Example 41.

Example 42 Preparation of Compound

A mixture of diBoc protected napthalene, Intermediate a of Example 42(20 mg, 0.07 mmol) in a mixture of TFA/CH₂Cl₂ (0.5/0.5 mL) was set atroom temperature overnight. All TFA/CH₂Cl₂ were removed under reducedpressure, the residue was purified with flash column (SiO₂, 3%NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product to give the desiredproduct as a white solid (17 mg). ¹H NMR (CD₃OD, 400 MHz) δ: 1.41 (s,9H), 4.89 (s, 2H), 7.36-7.56 (m, 5H), 7.6-8.0 (m, 5H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a mixture of alcohol (106 mg, 0.364 mmol), di-Bocguanidine (132 mg,0.52 mmol) and Ph₃P (100 mg) in toluene (3 mL) at 0° C. under nitrogenwas added DIAD (0.1 mL). The reaction mixture was stirred at roomtemperature overnight. The reaction mixture was concentrated to an oilresidue. Purification with flash column (SiO₂, EtOAc/hexane 0-30%) gavethe desired product (104 mg). ¹H NMR (CDCl₃, 400 MHz) δ: 1.20 (s, 9H),1.43 (s, 9H), 1.46 (s, 9H), 5.77 (s, 2H), 7.18 (d, J=4.0 Hz, 1H),7.36-7.39 (m, 2H), 7.43-7.47 (m, 2H), 7.51-7.59 (m, 3H), 7.87 (d, J=8.0Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 9.5 (bs, 1H), 9.55 (bs, 1H).

Example 43 Preparation of Compound

To a cooled solution of di-Boc protected guanidine compound,Intermediate c in Example 43 (55 mg) in 1.5 mL CH₂CL₂ was added 1.5 mLtrifluoroacetic acid. Reaction was taken off ice bath and stirred atroom temperature for 2 hours then solvents were evaporated.Chromatography achieved using ISCO max gradient 10% MeOH/methylenechloride yielding product as a white solid (31 mg, 86% yield). ¹H NMR(400 MHz) (MeOD₄) δ 7.96 (d, J=8 Hz, 1H), 7.59-7.55 (m, 1H), 7.43-7.36(m, 2H), 7.34-7.28 (m, 5H), 4.84-4.82 (m, 2H), 3.62 (s, 3H). ¹³C NMR(100 MHz) (MeOD₄) δ 159.08, 158.84, 138.10, 134.98, 133.69, 133.24,132.89, 132.44, 128.62, 128.00, 127.26, 126.98, 126.52, 124.08, 118.46,118.42, 108.89, 56.25, 44.76.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a solution of 5-bromo-1-naphthaldehyde (500 mg) in 20 mL ethanol wasslowly added NaBH₄ (243 mg, 3 eq.), and reaction was stirred for 30minutes at room temperature. Acetone (2 ml) was then added and solutionwas filtered through filter paper. Filtrate was concentrated thenre-dissolved in methylene chloride and washed with H₂O. The organiclayer was dried over sodium sulfate and concentrated to yield pureproduct as a white solid (473 mg, 94% yield). ¹H NMR (400 MHz) (CDCl₃) δ8.19-8.17 (m, 1H), 8.04 (d, J=8 Hz, 1H), 7.75-7.73 (m, 1H), 7.51-7.46(m, 2H), 7.33-7.29 (m, 1H), 5.08 (d, J=8 Hz, 2H). ¹³C NMR (100 MHz)(CDCl₃) δ136.71, 132.59, 132.38, 130.10, 127.76, 126.80, 126.58, 126.17,123.62, 63.63.

b. Preparation of Compound

(5-Bromonaphthalen-1-yl)methanol (275 mg), PPh₃ (456 mg, 1.5 eq.), and1,3-bis(t-butoxycarbonyl)guanidine (601 mg, 2 eq.) in 5 mL toluene at 0°C. was added diisopropylazodicarboxylate (0.34 mL, 1.5 eq.) drop wiseover 15 minutes. Reaction was stirred for 3 hours at room temperaturethen 2 drops H₂O were added, and the solution was concentrated.Chromatography achieved using ISCO max gradient 20% EtOAc/hexaneyielding product as a white solid (493 mg, 90% yield). ¹H NMR (400 MHz)(CDCl₃) δ 9.47 (bs, 2H), 8.11 (d, J=8 Hz, 1H), 7.91 (d, J=8 Hz, 1H),7.73 (d, J=8 Hz, 1H), 7.46 (t, J=16 Hz, 1H), 7.28 (t, J=16 Hz, 1H), 7.16(d, J=8 Hz, 1H), 5.62 (s, 2H), 1.36 (s, 9H), 1.07 (s, 9H). ¹³C NMR (100MHz) (CDCl₃) δ160.83, 154.95, 135.04, 131.95, 129.89, 126.71, 126.26,126.16, 123.71, 122.87, 122.73, 84.19, 79.03, 45.10, 28.23, 27.61.

c. Preparation of Compound

Intermediate b of Example 43, the Di-boc guanidine compound (100 mg),2-methoxy-4-trifluoromethylphenylboronic acid (55 mg, 1.2 eq.), Pd(OAc)₂(5 mg, 0.1 eq.), Xphos (20 mg, 0.2 eq.), and K₂CO₃ (87 mg, 3 eq.) werecombined in a flask with 3 mL dioxane and 1 mL H₂O and degassed.Reaction mixture was then refluxed at 100° C. for 2 hours. Solution wascooled to room temperature then diluted with EtOAc and washed withsaturated NaHCO₃. The organic layer was dried over sodium sulfate andconcentrated. Chromatography achieved using ISCO max gradient 15%EtOAc/hexane yielding product as a clear oil (55 mg, 46% yield). ¹H NMR(400 MHz) (CDCl₃) δ 9.55 (bs, 1H), 9.48 (bs, 1H), 8.08 (d, J=12 Hz, 1H),7.61-7.57 (m, 1H), 7.42-7.33 (m, 5H), 7.27 (s, 1H), 7.19 (d, J=4 Hz,1H), 5.86-5.70 (m, 2H), 3.75 (s, 3H), 1.47 (s, 9H), 1.21 (s, 9H). ¹³CNMR (100 MHz) (CDCl₃) δ163.81, 160.94, 157.44, 155.13, 136.18, 134.66,132.17, 131.88, 126.96, 125.30, 124.98, 123.00, 121.92, 84.04, 78.96,55.76, 45.37, 28.25, 27.61.

Example 44 Preparation of Compound

A flask was charged with LAH (15.6 mg, 2 eq.) in 3 mL anhydrous ether.To the suspension was added2-(5-(2-methoxy-4-(trifluoromethyl)phenyl)naphthalen-1-yl)acetonitrile(70 mg) in 2 mL anhydrous ether drop wise. Reaction was stirred at roomtemperature for 30 minutes then placed on an ice bath. H₂O (10 drops)was carefully dropped in to react with the remaining LAH then 1M NaOHwas added to get solution to pH>9. Solution was then diluted withadditional ether and extracted from aqueous. The organic layer was driedover sodium sulfate and concentrated. Chromatography achieved using ISCOmax gradient 10% MeOH/methylene chloride yielding product as clear oil(31 mg, 44% yield). ¹H NMR (400 MHz) (CDCl₃) δ 8.15 (d, J=8 Hz, 1H),7.62-7.58 (m, 1H), 7.43-7.32 (m, 6H), 7.28 (s, 1H), 3.77 (s, 3H),3.33-3.29 (m, 2H), 3.19 (t, J=12 Hz, 2H). ¹³C NMR (100 MHz) (CDCl₃)δ157.47, 136.32, 135.94, 133.69, 132.31, 132.23, 132.04, 126.98, 126.78,125.49, 125.24, 124.98, 123.94, 117.39, 117.36, 107.73, 55.78, 42.89,37.45.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

(5-Bromonaphthalen-1-yl)methanol (150 mg),2-methoxy-4-trifluoromethylphenylboronic acid (167 mg, 1.2 eq.),Pd(OAc)₂ (14 mg, 0.1 eq.), Xphos (60 mg, 0.2 eq.), and K₂CO₃ (262 mg, 3eq.) were combined in a flask with 5 mL dioxane and 1.6 mL H₂O anddegassed. Reaction mixture was then refluxed at 100° C. for 2 hours.Solution was cooled to room temperature then diluted with EtOAc andwashed with saturated NaHCO₃. The organic layer was dried over sodiumsulfate and concentrated. Chromatography achieved using ISCO maxgradient 35% EtOAc/hexane yielding product as a clear oil (55 mg, 86%yield). ¹H NMR (400 MHz) (CDCl₃) δ 8.24-8.22 (m, 1H), 7.64 (dd, J=8 Hz,J=8 Hz, 1H), 7.55 (d, J=8 Hz, 1H), 7.51 (d, J=8 Hz, 1H), 7.45-7.37 (m,4H), 7.29 (s, 1H), 5.22 (s, 2H), 3.76 (s, 3H). ¹³C NMR (100 MHz) (CDCl₃)δ157.45, 136.48, 136.27, 133.49, 132.21, 132.16, 131.47, 131.29, 131.15,127.29, 126.61, 125.77, 125.48, 125.41, 123.88, 122.79, 117.44, 117.40,107.72, 63.94, 55.76.

b. Preparation of Compound

To a solution of(5-(2-methoxy-4-(trifluoromethyl)phenyl)naphthalene-1-yl)methanol (180mg) and Et₃N (0.15 mL, 2 eq.) in 5 mL methylene chloride was added MsCl(0.06 mL, 1.5 eq.), and the reaction mixture was stirred overnight atroom temperature. Reaction was then diluted with methylene chloride andwashed with saturated NaHCO₃. The organic layer was dried over sodiumsulfate and concentrated. No further purification required, crudeproduct was taken to next step.

c. Preparation of Compound

(5-(2-Methoxy-4-(trifluoromethyl)phenyl)naphthalene-1-yl)methylmethanesulfonate (150 mg) was combined with KCN (48 mg, 2 eq.) in 3 mLanhydrous DMF and stirred at room temperature overnight. Reactionmixture was then diluted with EtOAc and washed with 10% LiCl solution.The organic layer was dried over sodium sulfate and concentrated.Chromatography achieved using ISCO max gradient 30% EtOAc/hexaneyielding product as clear oil (125 mg, quanitative). ¹H NMR (400 MHz)(CDCl₃) δ 7.97 (d, J=12 Hz, 1H), 7.72-7.68 (m, 1H), 7.63 (d, J=8 Hz,1H), 7.56 (d, J=8 Hz, 1H), 7.47 (d, J=4 Hz, 1H), 7.44-7.40 (m, 3H), 7.30(s, 1H), 4.21 (s, 2H), 3.77 (s, 3H). ¹³C NMR (100 MHz) (CDCl₃) δ157.41,136.80, 133.01, 132.18, 132.16, 130.87, 127.20, 126.56, 126.50, 126.06,125.53, 122.57, 117.66, 117.50, 117.46, 107.80, 107.77, 55.76, 22.01.

Example 45 Preparation of Compound

To a cooled solution of Intermediate a of Example 45, the di-Bocprotected guanidine compound (35 mg) in 1 mL methylene chloride wasadded 1 mL trifluoroacetic acid. Reaction was taken off ice bath andstirred at room temperature for 2 hours then solvents were evaporated.Chromatography achieved using ISCO max gradient 10% MeOH/methylenechloride yielding product as a clear oil (19 mg, 83% yield). ¹H NMR (400MHz) (MeOD₄) δ 8.16 (d, J=12 Hz, 1H), 7.66-7.62 (m, 1H), 7.44-7.34 (m,7H), 3.74 (s, 3H), 3.65 (t, J=16 Hz, 2H), 3.46-3.42 (m, 2H). ¹³C NMR(100 MHz) (MeOD₄) δ159.10, 158.71, 138.00, 135.51, 135.25, 133.71,133.29, 133.18, 128.27, 128.09, 127.01, 126.76, 126.64, 126.58, 124.49,118.39, 118.35, 108.83, 56.23, 43.18, 33.14.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

2-(5-(2-Methoxy-4-(trifluoromethyl)phenyl)naphthalen-1-yl)ethanamine (25mg), 1,3-di-Boc-2-(trifluoromethylsulfonyl)-guanidine (34 mg, 1.2 eq.),and Et₃N (0.01 mL, 1.2 eq.) in 2.5 mL methylene chloride were stirred atroom temperature overnight. Reaction mixture was then diluted withmethylene chloride and washed with NaHCO₃. The organic layer was driedover sodium sulfate and concentrated. Chromatography achieved using ISCOmax gradient 30% EtOAc/hexane yielding product as a clear oil (37 mg,88% yield). ¹H NMR (400 MHz) (CDCl₃) δ 11.50 (bs, 1H), 8.50 (t, J=12 Hz,1H), 8.38 (d, J=8 Hz, 1H), 7.62 (dd, J=8 Hz, J=8 Hz, 1H), 7.43-7.36 (m,5H), 7.35-7.31 (m, 1H), 7.27 (s, 1H), 3.85-3.79 (m, 2H), 3.76 (s, 3H),3.50-3.37 (m, 2H), 1.57 (s, 9H), 1.51 (s, 9H). ¹³C NMR (100 MHz) (CDCl₃)δ163.67, 157.50, 156.14, 153.21, 136.15, 134.95, 133.77, 132.24, 132.05,127.08, 126.75, 125.49, 125.46, 125.30, 124.34, 117.33, 83.03, 79.10,55.77, 41.78, 32.96, 28.38, 28.06.

Example 46 Preparation of Compound

To a cooled solution of Intermediate b of Example 46, di-Boc protectedguanidine compound (35 mg) in 1 mL methylene chloride was added 1 mLtrifluoroacetic acid. Reaction was taken off ice bath and stirred atroom temperature for 2 hours then solvents were evaporated.Chromatography achieved using ISCO max gradient 10% MeOH/methylenechloride yielding product as a tan solid (18 mg, 20% yield over 2steps). ¹H NMR (400 MHz) (MeOD₄) δ 8.02-8.00 (m, 1H), 7.90-7.88 (m, 1H),7.67-7.63 (m, 1H), 7.54-7.50 (m, 1H), 7.47-7.42 (m, 1H), 7.33-7.31 (m,2H), 7.24-7.22 (m, 2H), 4.93 (s, 2H), 2.06-1.99 (m, 1H), 1.06-1.02 (m,2H), 0.79-0.76 (m, 2H). ¹³C NMR (100 MHz) (MeOD₄) δ158.85, 144.86,142.73, 139.06, 133.62, 132.84, 130.95, 129.42, 128.20, 128.13, 127.31,126.69, 126.63, 126.38, 123.27, 44.69, 15.98, 9.74.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

(5-(4-Bromophenyl)naphthalen-1-yl)methanol (130 mg), cyclopropylboronicacid (71 mg, 2 eq.), Pd(OAc)₂ (5 mg, 0.05 eq.), tricyclohexylphosphine(12 mg, 0.1 eq.), and K₂PO₄ (308 mg, 3.5 eq.) were combined in a flaskwith 3 mL toluene and 1 mL H₂O and degassed. Reaction mixture was thenrefluxed at 100° C. for 3 hours. Solution was cooled to room temperaturethen diluted with EtOAc and washed with saturated NaHCO₃. The organiclayer was dried over sodium sulfate and concentrated. Chromatographyachieved using ISCO max gradient 35% EtOAc/hexane yielding product as abrown oil (86 mg, 75% yield). ¹H NMR (400 MHz) (CDCl₃) δ 8.17-8.15 (m,1H), 7.96-7.94 (m, 1H), 7.61 (dd, J=8 Hz, J=8 Hz, 1H), 7.56-7.53 (m,2H), 7.49-7.47 (m, 1H), 7.43-7.40 (m, 2H), 7.25-7.23 (m, 2H), 5.19 (s,2H), 2.08-2.01 (m, 1H), 1.11-1.06 (m, 2H), 0.87-0.83 (m, 2H). ¹³C NMR(100 MHz) (CDCl₃) δ143.16, 141.02, 138.03, 136.48, 132.17, 131.62,130.13, 130.05, 138.27, 126.80, 125.84, 125.55, 125.36, 125.27, 123.00,63.90, 15.28, 9.41.

b. Preparation of Compound

(5-(4-Cyclopropylphenyl)naphthalen-1-yl)methanol (80 mg), PPh₃ (115 mg,1.5 eq.), and 1,3-bis(t-butoxycarbonyl)guanidine (151 mg, 2 eq.) in 3 mLtoluene at 0° C. was added diisopropylazodicarboxylate (0.09 mL, 1.5eq.) drop wise over 15 minutes. Reaction was stirred for 3 hours at roomtemperature then 2 drops H₂O were added, and the solution wasconcentrated. Solid was then re-dissolved in methylene chloride andpassed through silica column and resulting crude product was taken tonext step.

Example 47 Preparation of Compound

To a cooled solution of di-Boc protected guanidine compound (80 mg) in 1mL methylene chloride was added 1 mL trifluoroacetic acid. Reaction wastaken off ice bath and stirred at room temperature for 2 hours then thesolvents were evaporated. Chromatography achieved using ISCO maxgradient 10% MeOH/methylene chloride yielding product as a clear oil (50mg, quantitative). ¹H NMR (400 MHz) (MeOD₄) δ 8.11 (d, J=8 Hz, 1H),7.74-7.69 (m, 2H), 7.64 (d, J=8 Hz, 1H), 7.57-7.55 (m, 1H), 7.47-7.37(m, 4H), 4.96 (m, 2H), 2.06 (s, 3H). ¹³C NMR (100 MHz) (MeOD₄) δ158.91,145.64, 140.57, 139.28, 133.32, 132.63, 131.96, 127.97, 127.64, 127.40,127.38, 127.05, 126.88, 124.18, 123.65, 123.61, 44.55, 20.05.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

(5-Bromonaphthalen-1-yl)methanol (165 mg),2-methyl-4-trifluoromethylphenylboronic acid (170 mg, 1.2 eq.),Pd(PPh₃)₄ (80 mg, 0.1 eq.), and K₂CO₃ (288 mg, 3 eq.) were combined in aflask with 5 mL dioxane and 2.5 mL H₂O and degassed. Reaction mixturewas then refluxed at 100° C. overnight. Solution was cooled to roomtemperature then diluted with EtOAc and washed with saturated NaHCO₃.The organic layer was dried over sodium sulfate and concentrated.Chromatography achieved using ISCO max gradient 30% EtOAc/hexaneyielding product as a yellow oil (208 mg, 95% yield). ¹H NMR (400 MHz)(CDCl₃) δ 8.24 (d, J=8 Hz, 1H), 7.65-7.64 (m, 1H), 7.63-7.56 (m, 2H),7.40-7.36 (m, 5H), 5.23 (s, 2H), 2.10 (s, 3H). ¹³C NMR (100 MHz) (CDCl₃)δ144.16, 139.06, 137.81, 136.68, 131.92, 131.42, 130.74, 126.63, 126.51,126.20, 125.82, 125.56, 123.73, 122.52, 122.48, 63.84, 20.06.

b. Preparation of Compound

(5-(2-Methyl-4-(trifluoromethyl)phenyl)naphthalen-1-yl)methanol (67 mg),PPh₃ (83 mg, 1.5 eq.), and 1,3-bis(t-butoxycarbonyl)guanidine (110 mg, 2eq.) in 3 mL toluene at 0° C. was added diisopropylazodicarboxylate(0.06 mL, 1.5 eq.) drop wise over 15 minutes. Reaction was stirred for 3hours at room temperature then 2 drops H₂O were added, and the solutionwas concentrated. Chromatography achieved using ISCO max gradient 30%EtOAc/hexane yielding product as a clear oil (93 mg, 79% yield). ¹H NMR(400 MHz) (CDCl₃) δ 9.55 (bs, 2H), 8.10 (d, J=8 Hz, 1H), 7.62-7.57 (m,3H), 7.41-7.22 (m, 5H), 5.84-5.74 (m, 2H), 2.06 (s, 3H), 1.48 (s, 9H),1.17 (s, 9H). ¹³C NMR (100 MHz) (CDCl₃) δ163.80, 160.97, 155.04, 138.98,137.77, 135.08, 131.60, 130.85, 130.69, 126.61, 126.20, 125.71, 125.37,124.60, 122.88, 122.45, 122.23, 84.03, 78.99, 45.23, 28.26, 27.57,19.93.

Example 48 Preparation of Compound

1-(4-(t-butyl)phenyl)-2,3-dimethoxy-5-nitronaphthalene (1.159 g) wascombined with 3 mL hydrazine monohydrate and 200 mg Pd/C in 35 mLethanol and refluxed at 85° C. for 1.5 hours. Pd/C was then filtered outand filtrate concentrated yielding product as a pinkish-white solid(1.03 g, 97% yield). ¹H NMR (400 MHz) (CDCl₃) δ 7.41-7.39 (m, 2H),7.22-7.20 (m, 2H), 7.07 (s, 1H), 7.00-6.96 (m, 1H), 6.86 (d, J=8 Hz,1H), 6.67-6.65 (m, 1H), 3.94 (s, 3H), 3.54 (s, 3H), 1.33 (s, 9H). ¹³CNMR (100 MHz) (CDCl₃) δ 151.69, 149.88, 146.68, 133.25, 132.90, 130.11,130.01, 124.91, 124.19, 121.34, 117.88, 110.12, 100.37, 61.01, 55.77,34.64, 31.56.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

1-Bromo-2,3-dimethoxy-5-nitronaphthalene (1 g), 4-t-butylphenylboronicacid (685 mg, 1.2 eq.), Pd(PPh₃)₄ (370 mg, 0.1 eq.), and Na₂CO₃ (680 mg,2 eq.) were combined in a flask with 20 mL dioxane and 5 mL H₂O anddegassed. Reaction mixture was then refluxed at 100° C. overnight.Solution was cooled to room temperature then diluted with EtOAc andwashed with saturated NaHCO₃. The organic layer was dried over sodiumsulfate and concentrated. Chromatography achieved using ISCO maxgradient 20% EtOAc/hexane yielding product as a yellow solid (1.159 g,99% yield). ¹H NMR (400 MHz) (CDCl₃) δ 8.18 (dd, J=8 Hz, J=4 Hz, 1H),8.08 (s, 1H), 7.79-7.77 (m, 1H), 7.54 (dt, J=8 Hz, J=4 Hz, 2H), 7.30 (t,J=4 Hz, 1H), 7.28-7.27 (m, 2H), 3.99 (s, 3H), 3.58 (s, 3H), 1.34 (s,9H). ¹³C NMR (100 MHz) (CDCl₃) δ 155.05, 150.69, 147.53, 145.44, 132.89,132.72, 131.97, 130.66, 130.06, 125.26, 123.59, 123.54 121.87, 102.16,61.08, 55.91, 34.71, 31.43.

Example 49 Preparation of Compound

To a solution of the compound of Example 48 (120 mg) in 25.0 ml ofmethanol containing 0.17 ml para-formaldehyde was added solution ofNaCNBH₃ (45 mg) and ZnCl₂ (50 mg in 2.5 mL of MeOH). After the reactionis stirred for 12 hour, the solution was washed with dilute HCl andsaturated sodium bicarbonate to give the crude product which was thenpurified by flash column chromatography giving 67% desired product. ¹HNMR (CDCl₃, 400 MHz) δ: 2.94 (s, 6H), 3.86 (s, 3H), 4.09 (s, 3H), 7.10(d, J=8.0 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.30 (s, 1H), 7.40 (t, J=8.0Hz, 1H), 7.50 (t, J=8.0 Hz, 2H), 7.60 (d, J=8.0 Hz, 2H), 7.67 (s, 1H),7.73 (m, 4H).

Example 50 Preparation of Compound

Prepared from the compound of Example 49 by General Method B (72%yield); ¹H NMR (CDCl₃, 400 MHz) δ: 3.86 (s, 3H), 4.20 (s, 3H), 4.39 (s,9H), 7.42 (m, 4H), 7.51-7.55 (m, 4H), 7.72 (d, J=8.0 Hz, 2H), 7.80 (d,J=8.0 Hz, 3H).

Example 51 Preparation of Compound

A mixture of diBoc protected1-((5-(4-bromophenyl)naphthalen-1-yl)methyl)guanidine (34 mg, 0.06 mmol)in a mixture of TFA/CH₂Cl₂ (0.8/0.8 mL) was set at room temperatureovernight. All TFA/CH₂Cl₂ were removed under reduced pressure, theresidue was purified with flash column (SiO₂, 3% NH₄OH-MeOH/CH₂Cl₂0-20%) gave the desired product to give the desired product as a whitesolid (18 mg, 75%). ¹H NMR (DMSO, 300 MHz) δ: 4.90 (s, 2H), 7.12 (bs,4H), 7.52 (m, 2H), 7.67-7.75 (m, 2H), 8.06 (m, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a stirred mixture of 5-bromo-1-napthaldehyde (0.50 g, 2.12 mmol),diborane (0.81 g), KOAc (0.80 g) in DMF (10 mL) was added Pd(OAc)₂ (20mg). The reaction mixture was degassed for 5 min and heated at 80° C.for 6 h. The reaction mixture was diluted with EtOAc, washed with brineand was dried over MgSO₄ filtered and concentrated and purified withflash column (SiO₂, EtOAc/hexane 0-15%) to give the desired product asoil. ¹H NMR (CDCl₃, 300 MHz) δ: 1.46 (s, 12H), 7.69-7.73 (m, 2H), 8.01(d, J=8.0 Hz, 1H), 8.21 (d, J=8.0 Hz, 1H), 9.12 (d, J=8.0 Hz, 1H), 9.42(d, J=8.0 Hz, 1H), 10.4 (s, 1H).

b. Preparation of Compound

To a nitrogen-flushed mixture of pinacole boronate ester (0.209 g, 0.7mmol), 4-bromo iodobenzene (0.23) and potassium carbonate (0.20 g, 6.4mmol) in a mixture of dioxane (8 mL) and water (1.5 mL) at roomtemperature under nitrogen was addedtetrakis(triphenylphosphine)-palladium (40 mg, 5 mol %), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-50%) to give the desired product as a semi yellow solid (0.142 g,65%). ¹H NMR (CDCl₃, 300 MHz) δ: 7.36-7.39 (m, 2H), 7.55 (d, J=9.0 Hz,1H), 7.60-7.69 (m, 3H), 7.76 (m, 2H), 8.05 (d, J=9.0 Hz, 1H), 8.15 (d,J=9.0 Hz, 1H), 10.5 (s, 1H).

c. Preparation of Compound

A mixture of aldehyde (0.14 g, 0.45 mmol) and NaBH₄ (12 mg) in 95% EtOH(8 mL) was stirred at room temperature for 2 h. It was filtered and thefiltrate was concentrated and redissolved in CH₂Cl₂ (40 mL). The CH₂Cl₂solution was washed with aq. NaHCO₃ and brine, dried over over MgSO₄,filtered and concentrated. Purification with flash column (SiO₂,EtOAc/hexane 10-30%) gave the desired product (0.14 g, 100%). ¹H NMR(CDCl₃, 300 MHz) δ: 5.14 (s, 2H), 7.26-7.36 (m, 4H), 7.47-7.56 (m, 4H),7.74 (d, J=9.0 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H).

d. Preparation of Compound

To a mixture of (5-(4-bromophenyl)naphthalen-1-yl)methanol (40 mg, 0.128mmol), di-Boc guanidine (66 mg, 0.26 mmol) and Ph₃P (60 mg, 0.23 mmol)in toluene (3 mL) at 0° C. under nitrogen was added DIAD (0.04 mL, 0.20mmol). The reaction mixture was stirred at room temperature overnight.The reaction mixture was concentrated to an oil residue. Purificationwith flash column (SiO₂, EtOAc/hexane 0-30%) gave the desired product(34 mg, 47%). ¹H NMR (CDCl₃, 300 MHz) δ: 1.22 (s, 9H), 1.47 (s, 9H),5.78 (s, 2H), 7.21 (d, J=6.0 Hz, 1H), 7.37-7.66 (m, 7H), 7.75 (d, J=9.0Hz, 1H), 8.06 (d, J=9.0 Hz, 1H), 9.50 (bs, 1H), 9.60 (bs, 1H).

Example 52 Preparation of Compound

A mixture of diBoc protected napthalene (46 mg, 0.09 mmol) in a mixtureof TFA/CH₂Cl₂ (0.8/0.8 mL) was set at room temperature overnight. AllTFA/CH₂Cl₂ were removed under reduced pressure, the residue was purifiedwith flash column (SiO₂, 3% NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desiredproduct to give the desired product as a white solid (27 mg, 78%). ¹HNMR (DMSO, 300 MHz) δ: 4.89 (d, J=3.0 Hz, 2H), 7.46-7.53 (m, 4H),7.59-7.75 (m, 4H), 8.08 (m, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a nitrogen-flushed mixture of pinacole boronate ester (0.20 g, 0.7mmol), 4-chloro bromobenzene (0.16 g) and potassium carbonate (0.20 g,6.4 mmol) in a mixture of dioxane (6 mL) and water (1.5 mL) at roomtemperature under nitrogen was addedtetrakis(triphenylphosphine)-palladium (40 mg, 5 mol %), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane0-15%) to give the desired product as a pale solid (0.16 g, 84%). ¹H NMR(CDCl₃, 300 MHz) δ: 7.14-7.44 (m, 2H), 7.50-7.56 (m, 4H), 7.63 (m, 1H),7.77 (m, 1H), 8.06 (d, J=9.0 Hz, 1H), 8.15 (d, J=9.0 Hz, 1H).

b. Preparation of Compound

A mixture of 5-(4-chlorophenyl)-1-naphthaldehyde (0.16 g, 0.60 mmol) andNaBH₄ (16 mg) in 95% EtOH (10 mL) was stirred at room temperature for 1h. It was filtered and the filtrate was concentrated and redissolved inCH₂Cl₂ (40 mL). The CH₂Cl₂ solution was washed with aq. NaHCO₃ andbrine, dried over over MgSO₄, filtered and concentrated. Purificationwith flash column (SiO₂, EtOAc/hexane 10-30%) gave the desired product(0.16 g, 100%). ¹H NMR (CDCl₃, 300 MHz) δ: 5.23 (s, 2H), 7.42-7.52 (m,6H), 7.58-7.66 (m, 2H), 7.84 (d, J=9.0 Hz, 1H), 8.21 (d, J=9.0 Hz, 1H).

c. Preparation of Compound

To a mixture of (5-(4-chlorophenyl)naphthalen-1-yl)methanol (50 mg,0.186 mmol), di-Boc guanidine (96 mg) and Ph₃P (73 mg) in toluene (3 mL)at 0° C. under nitrogen was added DIAD (0.06 mL). The reaction mixturewas stirred at room temperature overnight. The reaction mixture wasconcentrated to an oil residue. Purification with flash column (SiO₂,EtOAc/hexane 0-30%) gave the desired product (46 mg, 48%). ¹H NMR(CDCl₃, 400 MHz) δ:1.21 (s, 9H), 1.47 (s, 9H), 5.80 (s, 2H), 7.21 (d,J=6.0 Hz, 1H), 7.37-7.61 (m, 7H), 7.75 (d, J=9.0 Hz, 1H), 8.06 (d, J=9.0Hz, 1H).

Example 53 Preparation of Compound

A mixture of diBoc protected napthalene, Intermediate c Example 53, (56mg, 0.1 mmol) in a mixture of TFA/CH₂Cl₂ (0.8/0.8 mL) was set at roomtemperature overnight. All TFA/CH₂Cl₂ were removed under reducedpressure, the residue was purified with flash column (SiO₂, 3%NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product to give the desiredproduct as a white solid (20 mg, 51%). ¹H NMR (CDCl₃, 300 MHz) δ: 4.97(s, 2H), 7.50-7.56 (m, 3H), 7.65-7.23 (m, 3H), 7.84 (m, 3H), 8.11 (d,J=6.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a nitrogen-flushed mixture of 5-bromo-1-napthaldehyde (0.50 g, 2.1mmol), 4-CF₃ phenylboronic acid (0.62 g) and potassium carbonate (0.88g, 6.4 mmol) in a mixture of dioxane (10 mL) and water (2 mL) at roomtemperature under nitrogen was addedtetrakis(triphenylphosphine)-palladium (73 mg, 0.06 mmol), the resultantmixture was heated at 100° C. for 5 h. It was dried over MgSO₄, filteredand concentrated and purified with flash column (SiO₂, EtOAc/hexane10-30%) to give the desired product as a pale solid (0.56 g, 88%). ¹HNMR (CDCl₃, 400 MHz) δ: 7.52 (d, J=8.0 Hz, 1H), 7.58-7.62 (m, 3H),7.73-7.78 (m, 3H), 8.01-8.08 (m, 2H), 9.35 (d, J=8.0 Hz, 1H), 10.45 (s,1H).

b. Preparation of Compound

A mixture of 5-(4-(trifluoromethyl)phenyl)-1-naphthaldehyde (0.35 g,1.16 mmol) and NaBH₄ (31 mg) in 95% EtOH (15 mL) was stirred at roomtemperature for 1 h. It was filtered and the filtrate was concentratedand redissolved in CH₂Cl₂ (40 mL). The CH₂Cl₂ solution was washed withaq. NaHCO₃ and brine, dried over over MgSO₄, filtered and concentrated.Purification with flash column (SiO₂, EtOAc/hexane 10-30%) gave thedesired product as a white solid (0.35 g). ¹H NMR (CDCl₃, 300 MHz) δ:5.15 (s, 2H), 7.4 (m, 2H), 7.56 (m, 4H), 7.7 (m, 3H), 8.16 (d, J=6.0 Hz,1H).

c. Preparation of Compound

To a mixture of (5-(4-(trifluoromethyl)phenyl)naphthalen-1-yl)methanol(40 mg, 0.13 mmol), di-Bocguanidine (70 mg) and Ph₃P (55 mg) in toluene(3 mL) at 0° C. under nitrogen was added DIAD (0.04 mL). The reactionmixture was stirred at room temperature overnight. The reaction mixturewas concentrated to an oil residue. Purification with flash column(SiO₂, EtOAc/hexane 0-30%) gave the desired product as a white solid (56mg, 80%). ¹H NMR (CDCl₃, 400 MHz) δ: 1.12 (s, 9H), 1.37 (s, 9H), 5.68(s, 2H), 7.12 (d, J=4.0 Hz, 1H), 7.28-7.35 (m, 2H), 7.48-7.53 (m, 3H),7.61 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 2H), 8.00 (d, J=8.0 Hz, 1H),9.44 (bs, 2H).

Example 54 Preparation of Compound

To a stirred solution of(E)-1-(2-nitrovinyl)-5-(4-(trifluoromethyl)phenyl)naphthalene (0.21 g,0.62 mmol) in THF (10 mL) at room temperature was added LAH slowly. Thereaction mixture was stirred at room temperature overnight. After normalLAH work-up and the evaporation of the solvent gave the desired productas pale solid. ¹H NMR (CDCl₃, 300 MHz) δ: 3.23 (m, 2H), 3.36 (m, 2H),7.37-7.44 (m, 3H), 7.57-7.63 (m, 3H), 7.71-7.80 (m, 3H), 8.16 (d, J=9.0Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A mixture of 5-(4-(trifluoromethyl)phenyl)-1-napthaldehyde (0.20 g),NH₄OAc (60 mg) in nitromethane (3.0 mL) was heated to reflux for 6 h.Excess nitromethane was removed and the crude mixture was purified bycolumn chromatography using 5-10% EtOAc/hexane to afford a yellowproduct (0.21 g, 91%). ¹H NMR (CDCl₃, 300 MHz) δ: 7.41 (m, 2H), 7.52 (d,J=8.0 Hz, 2H), 7.58-7.65 (m, 2H), 7.70 (m, 3H), 7.88 (d, J=8.0 Hz, 1H),8.13 (d, J=8.0 Hz, 1H), 8.82 (d, J=16.0 Hz, 1H).

Example 55 Preparation of Compound

A mixture of diBoc protected napthalene, Intermediate a of Example 55(20 mg, 0.036 mmol) in a mixture of TFA/CH₂Cl₂ (0.5/0.5 mL) was set atroom temperature overnight. All TFA/CH₂Cl₂ were removed under reducedpressure, the residue was purified with flash column (SiO₂, 3%NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product to give the desiredproduct as a white solid (10.5 mg). ¹H NMR (CDCl₃, 300 MHz) δ: 3.46 (t,J=6.0 Hz, 2H), 3.66 (t, J=6.0 Hz, 2H), 7.43-7.51 (m, 3H), 7.64-7.73 (m,4H), 7.84 (d, J=6.0 Hz, 2H), 8.21 (d, J=6.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a stirred solution of2-(5-(4-(trifluoromethyl)phenyl)napthalen-1-yl)ethanamine (25 mg, 0.08mmol), triethylamine (0.03 mL) in methylene chloride (6 mL) was addeddiBoc guanidine triflate (40 mg) under nitrogen. The reaction mixturewas stirred overnight at room temp. The reaction mixture wasconcentrated to an oil residue. Purification with flash column (SiO₂,EtOAc/hexane 10-30%) gave the desired product (20 mg, 44%). ¹H NMR(CDCl₃, 300 MHz) δ: 1.50 (s, 9H), 1.56 (s, 9H), 3.44 (t, J=6.0 Hz, 2H),3.81 (m, 2H), 7.35-7.44 (m, 3H), 7.60-7.78 (m, 6H), 8.4-8.5 (m, 3H).

Example 56 Preparation of Compound

A mixture of 2-(5-(4-(t-butyl)phenyl)napthalen-1-yl)acetonitrile (0.12g, 0.4 mmol), in Et₂O (2 mL) was treated with 4N HCl/dioxane (2 mL), andwas stirred at 0° C. for 4 h. The mixture was then put into therefrigerator overnight. The solid thus formed was filtered and thentreated with NH₄OH/EtOH (6 mL) and heated to reflux for 6 h. Thereaction mixture was concentrated to dryness and was subjected to columnchromatography using 3% NH₄OH/MeOH/methylene chloride (0-20%) to givethe desired product (37 mg, 29%). ¹H NMR (CD₃OD, 300 MHz) δ: 1.44 (s,9H), 4.41 (s, 2H), 7.40 (m, 1H), 7.45-7.52 (m, 3H), 7.57-7.59 (m, 3H),7.68 (m, 1H), 7.96 (m, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a solution of (5-(4-(t-butyl)phenyl)napthalen-1-yl)methanol (0.60 g,2.0 mmol) in dry methylene chloride (12 ml) at 0° C. under nitrogen wasadded drop wise PBr₃ (0.40 mL). The reaction mixture was stirred at 0°C. for 1 h. The reaction was quenched by the addition of sodiumbicarbonate and extracted with methylene chloride. The solvent was thenremoved to give product as pale oil (0.67 g, 86%). ¹H NMR (CDCl₃, 300MHz) δ: 1.45 (s, 9H), 5.06 (s, 2H), 7.36-7.46 (m, 3H), 7.50-7.60 (m,3H), 7.69 (m, 2H), 8.00 (d, J=9.0 Hz, 1H), 8.21 (d, J=9.0 Hz, 1H).

b. Preparation of Compound

A mixture of 1-(bromomethyl)-5-(4-(tert-butyl)phenyl)naphthalene (0.20g, 0.57 mmol), and KCN (55 mg) in DMSO (6 mL) was stirred at roomtemperature overnight. The reaction mixture was diluted with water andwas extracted with diethyl ether. The crude product was then purified bycolumn chromatography using EtOAc/hexane (20%) to afford the product assolid (0.12 g, 74%). ¹H NMR (CDCl₃, 300 MHz) δ: 1.41 (s, 9H), 4.19 (s,2H), 7.39-7.44 (m, 3H), 7.50-7.53 (m, 3H), 7.61 (d, J=6.0 Hz, 1H), 7.66(d, J=6.0 Hz, 1H), 7.88 (d, J=6.0 Hz, 1H), 7.97 (d, J=9.0 Hz, 1H).

Example 57 Preparation of Compound

A mixture of 2-(5-(4-(CF₃)phenyl)napthalen-1-yl)acetonitrile (0.10 g,0.32 mmol), in Et₂O (2.0 mL) was treated with 4N HCl/dioxane (2.0 mL),and was stirred at 0° C. for 4 h. The mixture was then put into therefrigerator overnight. The solid thus formed was filtered and thentreated with NH₄OH/EtOH (5 mL) and heated to reflux for 8 h. Thereaction mixture was concentrated to dryness and was subjected to columnchromatography using 3% NH₄OH/MeOH/methylene chloride (0-20%) to givethe desired product (22 mg, 20%). ¹H NMR (CDCl₃, 300 MHz) δ: 4.44 (s,2H), 7.50-7.62 (m, 4H), 7.67-7.76 (m, 3H), 7.86 (d, J=9.0 Hz, 2H), 8.06(d, J=6.0 Hz, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

To a solution of (5-(4-(CF₃)phenyl)napthalen-1-yl)methanol (0.30 g, 0.99mmol) in dry methylene chloride (10 ml) at 0° C. under nitrogen wasadded drop-wise PBr₃ (0.14 mL). The reaction mixture was stirred at 0°C. for 1 h. The reaction was quenched by the addition of sodiumbicarbonate and extracted with methylene chloride. The solvent was thenremoved to give product as pale gum and used for the next step as crude.

b. Preparation of Compound

A mixture of 1-(bromomethyl)-5-(4-(CF₃)phenyl)naphthalene (0.30 g), andKCN (100 mg) in DMSO (8.0 mL) was stirred at room temperature overnight.The reaction mixture was diluted with water and was extracted withdiethyl ether. The crude product was then purified by columnchromatography using EtOAc/hexane (20%) to afford the product as solid(0.26 g, 84%). ¹H NMR (CDCl₃, 300 MHz) δ: 4.18 (s, 2H), 7.46-7.55 (m,2H), 7.62-7.75 (m, 4H), 7.80-7.88 (m, 3H), 7.99 (m, 1H).

Example 58 Preparation of Compound

A mixture of diBoc protected starting material, Intermediate f ofExample 58 (18 mg) in a mixture of TFA/CH₂Cl₂ (0.8/0.8 mL) was set atroom temperature overnight. All TFA/CH₂Cl₂ were removed under reducedpressure, the residue was purified with flash column (SiO₂, 3%NH₄OH-MeOH/CH₂Cl₂ 0-20%) gave the desired product to give the desiredproduct as a white solid (10 mg). ¹H NMR (CDCl₃, 400 MHz) δ: 1.34 (S,9H), 3.48 (S, 3H), 3.82 (S, 3H), 4.62 (bs, 2H), 6.71 (M, 1H), 6.80 (M,1H), 7.35 (M, 3H), 7.44 (M, 2H), 7.52 (M, 2H), 7.90 (M, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A solution of titanium tetrachloride (2.1 mL, 2.1 mmol) anddichloromethyl ether (0.1 mL) was stirred at 0° C. for 15 minutes. Asolution of 2-hydroxy-5-bromonapthalene (223 mg, 1.0 mmol) in 3.0 mL ofmethylene chloride was added drop wise, the solution was allowed to warmto room temperature and stirred for 12 h. 10 mL of 1N HCl was added, andthe mixture was extracted with methylene chloride. The organic layer waswashed with water, dried and evaporated to give crude product. Silicagel chromatography produced 120 mg of the desired product. ¹H NMR(CDCl₃, 400 MHz) δ: 7.25 (d, J=8.0 Hz, 1H), 7.46 (t, J=8.0 Hz, 1H), 7.74(d, J=8.0 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H), 8.47 (d, J=8.0 Hz, 1H), 10.8(S, 1H), 13.2 (S, 1H).

b. Preparation of Compound

A mixture of 2-hydroxy-5-bromo-1-naphthaldehyde (120 mg),4-t-butylphenylboronic acid (2 equiv.), Cs₂CO₃ (2 equiv.), Pd (PPh₃)₂Cl₂(5 mol %) in dioxane (3 mL) was subject to a microwave reactor for 15minutes. The crude reaction mixture was diluted with ethyl acetate andwas filtered through a plug of Celite and silica gel. The filtrate wasconcentrated under vacuo and was subjected to flash columnchromatography to afford the desired product (120 mg). ¹H NMR (CDCl₃,400 MHz) δ: 7.1 (d, J=8.0 Hz, 1H), 7.29-7.43 (M, 3H), 7.56 (M, 2H), 7.67(M, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.39 (d, J=8.0 Hz, 1H), 10.9 (S, 1H),13.2 (S, 1H).

c. Preparation of Compound

5-(4-t-Butylphenyl)-2-hydroxy-1-naphthaldehyde (113 mg) was dissolved indichloromethane to which added 2.0 equivalent of triethylamine and 1.5equivalent of Tf₂O at −78° C. After the reaction was complete, thereaction mixture was diluted with more methylene chloride which was thenwashed with saturated sodium bicarbonate and brine. The crude mixturewas then purified by flash column chromatography to afford the product(70 mg). ¹H NMR (CDCl₃, 400 MHz) δ: 1.34 (s, 9H), 7.29-7.34 (m, 3H),7.45 (m, 2H), 7.52 (d, J=4.0 Hz, 1H), 7.72 (m, 1H), 8.25 (d, J=12.0 Hz,1H), 9.11 (d, J=12.0 Hz, 1H), 10.76 (s, 1H).

d. Preparation of Compound

A mixture of 5-(4-t-butylphenyl)-1-formylnaphthalen-2-yltrifluoromethanesulfonate (60 mg), 2,3,4-trimethoxyphenylboronic acid(60 mg), Cs₂CO₃ (300 mg), Pd (PPh₃)₂Cl₂ (5 mol %) in dioxane (3 mL) wassubject to a micro wave reaction for 15 minutes. The crude reactionmixture was diluted with ethyl acetate and was filtered through a plugof Celite and silica gel. The filtrate was concentrated under vacuo andwas subjected to flash column chromatography to afford the desiredproduct (40 mg). ¹H NMR (CDCl₃, 400 MHz) δ: 3.65 (S, 3H), 3.97 (S, 6H),6.81 (d, J=8.0 Hz, 1H), 7.00 (d, J=8.0 Hz, 1H), 7.42-7.47 (M, 3H),7.54-7.57 (M, 3H), 7.72-7.76 (M, 1H), 8.22 (d, J=8.0 Hz, 1H), 9.35 (d,J=8.0 Hz, 1H), 10.24 (S, 1H).

e. Preparation of Compound

A mixture of5-(4-t-butylphenyl)-2-(2,3,4-trimethoxyphenyl)-1-naphthaldehyde (40 mg)and NaBH₄ (20 mg) in 95% EtOH (3 mL) was stirred at room temperature for1 h. After 1 h, acetone was added and the filtered solution wasconcentrated to give pure desired product as a white solid (35 mg). ¹HNMR (CDCl₃, 400 MHz) δ: 1.45 (S, 9H), 3.52 (S, 3H), 3.96 (S, 3H), 4.01(S, 3H), 4.71-4.74 (M, 1H), 5.09 (M, 1H), 6.84 (d, J=8.0 Hz, 1H), 7.00(d, J=8.0 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.47-7.56 (M, 4H), 7.69 (t,J=8.0 Hz, 1H), 8.00 (d, J=8.00 Hz, 1H), 8.43 (d, J=8.0 Hz, 1H).

f. Preparation of Compound

To a mixture of(5-(4-tert-butylphenyl)-2-(2,3,4-trimethoxyphenyl)naphthalen-1-yl)methanol(35 mg), di-Bocguanidine (42 mg) and Ph₃P (32 mg, 0.13 mmol) in toluene(3 mL) at 0° C. under nitrogen was added DIAD (0.02 mL, 0.10 mmol). Thereaction mixture was stirred at room temperature overnight. The reactionmixture was concentrated to an oil residue. Purification with flashcolumn (SiO₂, EtOAc/hexane 0-30%) gave the desired product (30 mg). ¹HNMR (CDCl₃, 400 MHz) δ: 1.34 (s, 18H), 1.48 (s, 9H), 3.64 (s, 3H), 3.81(s, 3H), 3.82 (s, 3H), 5.40 (d, J=12.0 Hz, 1H), 5.90 (d, J−16.0 Hz, 1H),6.54 (d, J=8.0 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 7.11 (d, J=8.0 Hz, 1H),7.37-7.48 (m, 6H), 7.80 (d, J=8.0 Hz, 1H), 8.10 (d, J−8.0 Hz, 1H), 8.48(bs, 1H), 8.99 (bs, 1H).

Example 59 Preparation of Compound

A 2-dram vial was added2-(1-(4-t-butylphenyl)naphthalen-6-yl)phenyl)methanesulfonate (18 mg,0.04 mmol), CH₃CN (1 mL), N,N-dimethylethane-1,2-diamine (36 mg, 0.4mmol). The sealed vial was heated to 80° C. for 12 h. After cooled toroom temperature, the reaction mixture was diluted with EtOAc (30 mL),washed with saturated NaHCO₃ (10 mL), brine (10 mL), dried over Na₂SO₄,concentrated in rotavapor and purified on silica gel. Elution withCH₂Cl₂ to (10/89/1: MeOH/CHCl₃/ammonium hydroxide) afforded the desiredcompound (8.0 mg, 45%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 7.92(d, 1H, J=8.64 Hz), 7.82 (d, 1H, J=1.20 Hz), 7.78 (d, 1H, J=8.08 Hz),7.36-7.50 (m, 8H), 7.25-7.32 (m, 3H), 3.72 (s, 2H), 2.48 (t, 2H, J=6.12Hz), 2.22 (t, 2H, J=6.12 Hz), 2.00 (s, 6H), 1.35 (s, 9H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with 5-bromonaphthalen-2-ol(500 mg, 2.24 mmol), 4-t-butylphenylboronic acid (600 mg, 3.36 mmol),water/dioxane (4 mL/16 ml), K₂CO₃ (68 mg, 4.46 mmol). The resultingsolution was degassed for 5 min, then Pd(PPh₃)₄ (130 mg, 0.112 mmol) wasadded. The reaction mixture was warmed to 90° C. and stirred for 3 h.After cooled to room temperature, the reaction mixture was diluted withEtOAc (60 mL) and washed with saturated NaHCO₃ (20 mL), brine (20 mL),dried over NaSO₄. The organic layer was concentrated in rotavapor andpurified on silica gel. Elution with 10% EtOAc/hexanes afforded thedesired compound (570 mg, 92%) as an off white solid. ¹H NMR (CDCl₃, 400MHz) δ 7.87 (d, 1H, J=9.16 Hz), 7.68 (d, 1H, J=7.68 Hz), 7.40-7.51 (m,5H), 7.20-7.28 (m, 2H), 7.04 (dd, 1H, J=2.60, 9.16 Hz), 5.03 (s, 1H),1.41 (s, 9H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with 5-(4-t-butylphenyl)naphthalen-2-ol (570 mg,2.06 mmol), CH₂Cl₂ (10 mL), and triethylamine (0.78 ml, 5.58 mmol).After cooling to −70° C., triflic anhydride (0.52 ml, 3.07 mmol) wasadded via a syringe over 5 min, then stirred at −70° C. for 30 min. Thereaction mixture was diluted with CH₂Cl₂ (60 mL) and washed withsaturated NaHCO₃ (20 ml), brine (20 mL), dried over Na₂SO₄, concentratedin rotavapor and purified on silica gel. Elution with 5% EtOAc/hexanesafforded the desired compound (802 mg, 95%) as a white solid. ¹H NMR(CDCl₃, 400 MHz) δ 8.07 (d, 1H, J=9.32 Hz), 7.88 (d, 1H, J=8.20 Hz),7.40-7.51 (m, 5H), 7.82 (d, 1H, J=2.52 Hz 7.64 (t, 1H, J=7.84 Hz),7.52-7.56 (m, 3H), 7.41-7.43 (m, 2H), 7.32 (dd, 1H, J=2.56, 9.32 Hz),1.44 (s, 9H).

c. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-t-butylphenyl)naphthalen-6-yl trifluoromethanesulfonate (280 mg,0.69 mmol), 2-formalphenylboronic acid (123 mg, 0.82 mmol),water/acetonitrile (2 mL/6 ml), K₂CO₃ (193 mg, 1.4 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (33 mg, 0.07mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (8.0mg, 0.03 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 2 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (50 mL)and washed with saturated NaHCO₃ (15 mL), brine (15 mL), dried overNa₂SO₄. The organic layer was concentrated in rotavapor and purified onsilica gel. Elution with 5% EtOAc/hexanes afforded the desired compound(182 mg, 73%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 9.98 (s, 1H),7.98-8.01 (m, 2H), 7.80-7.81 (m, 2H), 7.38-7.48 (m, 10H), 4.69 (s, 2H),1.35 (s, 9H).

d. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer was chargedwith 2-(1-(4-t-butylphenyl)naphthalen-6-yl)benzaldehyde (180 mg, 0.49mmol), ethanol (95%, 5 mL), NaBH₄ (38 mg, 1.0 mmol) was added in oneportion. The reaction mixture was stirred at room temperature for 1 h.Acetone (1 mL) was added to the reaction mixture. After 20 min, thereaction mixture was concentrated and the residue was partitionedbetween EtOAc (50 mL) and 1 N HCl (15 mL). The organic layer was washedwith saturated NaHCO₃ (15 mL), brine (15 mL), dried over Na₂SO₄,concentrated in rotavapor and purified on silica gel. Elution with 10%EtOAc/hexanes afforded the desired compound (158 mg, 88%) as a whitesolid. ¹H NMR (CDCl₃, 400 MHz) δ 8.01 (d, 1H, J=8.68 Hz), 7.89 (s, 1H),7.86 (d, 1H, J=8.20 Hz), 7.52-7.60 (m, 4H), 7.38-7.48 (m, 7H), 4.69 (s,2H), 1.42 (s, 9H).

e. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with2-(1-(4-tert-butylphenyl)naphthalen-6-yl)phenylmethanol (140 mg, 0.38mmol), CH₂Cl₂ (5 mL), and triethylamine (0.11 ml, 0.76 mmol).Methanesulfonyl chloride (44 μL, 0.57 mmol) was added via a syringe. Theresulting reaction mixture was stirred at room temperature overnight.The reaction mixture was diluted with CH₂Cl₂ (30 mL) and washed withsaturated NaHCO₃ (10 ml), brine (10 mL), dried over Na₂SO₄, andconcentrated in rotavapor and purified on silica gel. Elution with 10%EtOAc/hexanes afforded the desired compound (170 mg, quantitative) as awhite solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.03 (d, 1H, J=8.72 Hz), 7.95 (d,1H, J=1.52 Hz), 7.37-7.60 (m, 11H), 4.58 (s, 2H), 2.20 (s, 3H), 1.42 (s,9H).

Example 60 Preparation of Compound

A 2-dram vial was added2-(1-(4-tert-butylphenyl)naphthalen-6-yl)phenyl)methanesulfonate (18 mg,0.04 mmol), dimethylamine (2 M in THF, 2 mL)). The sealed vial washeated to 60° C. for 12 h. After cooled to room temperature, thereaction mixture was diluted with EtOAc (30 mL), washed with saturatedNaHCO₃ (10 mL), brine (10 mL), dried over Na₂SO₄, concentrated inrotavapor and purified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (10.0 mg,63%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 8.01 (d, 1H, J=8.64Hz), 7.94 (s, 1H), 7.89 (d, 1H, J=8.12 Hz), 7.40-7.62 (m, 8H), 7.33-7.44(m, 3H), 3.44 (s, 2H), 2.19 (s, 6H), 1.45 (s, 9H).

Example 61 Preparation of Compound

A 2-dram vial was added2-(1-(4-t-butylphenyl)naphthalen-6-yl)phenyl)methanesulfonate (18 mg,0.04 mmol), methanamine (2 M in THF, 2 mL)). The sealed vial was heatedto 60° C. for 12 h. After cooled to room temperature, the reactionmixture was diluted with EtOAc (30 mL), washed with saturated NaHCO₃ (10mL), brine (10 mL), dried over Na₂SO₄, concentrated in rotavapor andpurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (7.6 mg,50%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 7.93 (d, 1H, J=8.64Hz), 7.78-7.83 (m, 2H), 7.36-7.51 (m, 8H), 7.26-7.33 (m, 3H), 3.69 (s,2H), 2.24 (s, 3H), 1.35 (s, 9H).

Example 62 Preparation of Compound

A 2-dram vial was added2-(1-(4-t-butylphenyl)naphthalen-6-yl)phenyl)methanesulfonate (14 mg,0.03 mmol), CH₃CN (1 mL), ethane-1,2-diamine (20 mg, 0.3 mL). The sealedvial was heated to 60° C. for 12 h. After cooled to room temperature,the reaction mixture was diluted with EtOAc (30 mL), washed withsaturated NaHCO₃ (10 mL), brine (10 mL), dried over Na₂SO₄, concentratedin rotavapor and purified on silica gel. Elution with CH₂Cl₂ to(10/89/1: MeOH/CHCl₃/saturated NH₃ in water) afforded the desiredcompound (13 mg, quantitative) as colorless oil. ¹H NMR (CDCl₃, 400 MHz)δ 8.03 (d, 1H, J=8.64 Hz), 7.93 (d, 1H, J=1.20 Hz), 7.88 (d, 1H, J=8.08Hz), 7.48-7.60 (m, 8H), 7.35-7.43 (m, 3H), 3.82 (s, 2H), 2.70 (t, 2H,J=5.60 Hz), 2.58 (t, 2H, J=5.48 Hz), 1.45 (s, 9H).

Example 63 Preparation of Compound

A solution of(2-(1-(4-t-butylphenyl)naphthalen-6-yl)phenyl)-N,N-dimethylmethanamine(82.0 mg, 0.21 mmol) in iodomethane (1.5 mL) in a sealed 2-dram vial wasstirred at 50° C. overnight. After cooled to room temperature, Et₂O wasadded to the reaction mixture. The solid was collected by filtration.After triturated with Et₂O and dried, there was obtained the desiredcompound (70 mg, 63%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.11(d, 1H, J=8.68 Hz), 8.07 (d, 1H, J=7.64 Hz), 7.88 (d, 1H, J=7.96 Hz),7.81 (d, 1H, J=1.52 Hz), 7.45-7.65 (m, 9H), 7.32 (dd, 1H, J=1.84, 8.60Hz), 5.0 (s, 2H), 3.07 (s, 9H), 1.43 (s, 9H).

Example 64 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-t-butylphenyl)naphthalen-6-yl trifluoromethanesulfonate (55 mg,0.135 mmol), 3-(dimethylamino)phenylboronic acid (27 mg, 0.16 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (40 mg, 0.27 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (7 mg, 0.014mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0mg, 0.007 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 2 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (50 mL)and washed with saturated NaHCO₃ (15 mL), brine (15 mL), dried overNa₂SO₄. The organic layer was concentrated in rotavapor and purified onsilica gel. Elution with 5% EtOAc/hexanes afforded the desired compound(30 mg, 59%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.02 (d, 1H,J=1.60 Hz), 7.94 (d, 1H, J=8.68 Hz), 7.82 (d, 1H, J=8.20 Hz), 7.62 (dd,1H, J=1.64, 8.76 Hz), 7.26-7.48 (m, 7H), 6.98-7.01 (m, 2H), 6.71 (dd,1H, J=2.48, 8.28 Hz), 2.96 (s, 6H), 1.35 (s, 9H).

Example 65 Preparation of Compound

A solution of the3-(1-(4-t-butylphenyl)naphthalen-6-yl)-N,N-dimethylbenzenamine (30 mg,0.08 mmol) in iodomethane (1.0 mL) in a sealed 2-dram vial was stirredat 80° C. overnight. After cooled to room temperature, Et₂O was added tothe suspension. The solid was collected by filtration to afford thedesired compound (35 mg, 85%) as an off white solid. ¹H NMR (CDCl₃, 400MHz) δ 8.30 (d, 1H, J=1.72 Hz), 8.10-8.14 (m, 2H), 8.05 (d, 1H, J=8.28Hz), 7.88-7.95 (m, 2H), 7.68-7.78 (m, 2H), 7.48-7.64 (m, 6H), 4.14 (s,9H), 1.45 (s, 9H).

Example 66 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with the triflate (25 mg,0.06 mmol), 3-(dimethylamino)phenylboronic acid (14 mg, 0.07 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (17 mg, 0.12 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (5 mg, 0.01 mmol).The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0 mg,0.009 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 1.5 h. Aftercooled to room temperature, the reaction mixture was diluted with EtOAc(30 mL) and washed with saturated NaHCO₃ (10 mL), brine (10 mL), driedover Na₂SO₄. The organic layer was concentrated with a rotavapor andpurified on silica gel. Elution with 5% EtOAc/hexanes afforded thedesired compound (16 mg, 67%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 8.03 (d, 2H, J=1.52 Hz), 7.94 (d, 1H, J=8.80 Hz), 7.86 (d, 1H, J=8.20Hz), 7.58-7.70 (m, 5H), 7.25-7.52 (m, 8H), 7.67-7.01 (m, 2H), 6.69-6.72(m, 1H), 2.95 (s, 6H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-bromonaphthalen-2-ol (300 mg, 1.35 mmol), 3-biphenylboronic acid (523mg, 2.69 mmol), water/dioxane (4 mL/16 ml), K₂CO₃ (383 mg, 2.78 mmol).The resulting solution was degassed for 5 min, then Pd(PPh₃)₄ (77 mg,0.07 mmol) was added. The reaction mixture was heated to 100° C. for 12h. After cooled to room temperature, the reaction mixture was dilutedwith EtOAc (60 mL) and washed with saturated NaHCO₃ (20 mL), brine (20mL), dried over Na₂SO₄. The organic layer was concentrated in rotavaporand purified on silica gel. Elution with 10% EtOAc/hexanes afforded thedesired compound (323 mg, 81%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 7.90 (d, 1H, J=9.12 Hz), 7.67-7.75 (m, 5H), 7.59 (t, 1H, J=7.56 Hz),7.46-7.53 (m, 4H), 7.34-7.41 (m, 2H), 7.25 (d, 1H, J=2.56 Hz), 7.09 (dd,1H, J=2.56, 9.12 Hz), 5.20 (s, 1H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with the 5-(biphenyl-3-yl)naphthalen-2-ol (323 mg,1.09 mmol), CH₂Cl₂ (10 mL), and triethylamine (0.31 ml, 2.20 mmol).After cooling to −70° C., triflic anhydride (0.21 ml, 1.20 mmol) wasadded via a syringe. The resulting reaction mixture was stirred at −70°C. for 30 min, then room temperature for 30 min. The reaction mixturewas diluted with CH₂Cl₂ (50 mL) and washed with saturated NaHCO₃ (20ml), brine (20 mL), dried over Na₂SO₄, and concentrated in rotavapor andpurified on silica gel. Elution with 5% EtOAc/hexanes afforded thedesired compound (434 mg, 93%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 7.98 (d, 1H, J=9.32 Hz), 7.83 (d, 1H, J=8.16 Hz), 7.75 (d, 1H, J=2.56Hz), 7.48-7.65 (m, 7H), 7.36-7.42 (m, 3H), 7.27-7.33 (m, 1H), 7.25 (dd,1H, J=9.32, 2.65 Hz).

Example 67 Preparation of Compound

A solution of the compound of Example 66 (15 mg, 0.04 mmol) iniodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 80° C.overnight. After cooled to room temperature, the reaction mixture wasadded Et₂O. The solid was collected by filtration to afford the desiredcompound (18 mg, 90%) as a light yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ8.38 (s, 1H), 8.17 (s, 1H), 8.10-8.13 (m, 2H), 7.89-7.95 (m, 2H),7.36-7.76 (m, 13H), 4.14 (s, 9H).

Example 68 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with the triflate (25 mg,0.06 mmol), 4-(dimethylamino)phenylboronic acid (14 mg, 0.07 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (17 mg, 0.12 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (5 mg, 0.01 mmol).The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0 mg,0.009 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 1.5 h. Aftercooled to room temperature, the reaction mixture was diluted with EtOAc(30 mL) and washed with saturated NaHCO₃ (10 mL), brine (10 mL), driedover Na₂SO₄. The organic layer was concentrated on a rotavapor andpurified on silica gel. Elution with 5% EtOAc/hexanes afforded thedesired compound (20 mg, 83%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 7.98 (s, 1H), 7.90 (d, 1H, J=8.79 Hz), 7.82 (d, 1H, J=8.02 Hz),7.18-7.79 (m, 14H), 6.77-6.80 (m, 2H), 2.94 (s, 6H).

Example 69 Preparation of Compound

A solution of the compound of Example 68 (20 mg, 0.05 mmol) iniodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 80° C.overnight. After cooled to room temperature, Et₂O was added to thesuspension. The solid was collected by filtration to afford the desiredcompound (16 mg, 59%) as a light yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ8.15 (d, 1H, J=1.76 Hz), 8.11 (d, 1H, J=8.88 Hz), 8.04-8.06 (m, 2H),7.97-8.00 (m, 2H), 7.36-7.78 (m, 13H), 4.11 (s, 9H).

Example 70 Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with the startingmaterial cyano (82 mg, 0.21 mmol), THF/toluene (10 mL/10 mL). Aftercooled to 0° C., LiAlH₄ (30 mg, 0.79 mmol) was added to the reactionmixture. The reaction mixture was heated to 100° C. and stirred for 3 h.After cooled to 0° C., the reaction mixture was diluted with EtOAc (50mL) and quenched with 15% NaOH (0.24 mL), water (1 mL). The organiclayer was decanted, dried over Na₂SO₄, concentrated in rotavapor andpurified on silica gel. Elution with 5% MeOH/CH₂Cl₂ afforded the desiredcompound (25 mg, 30%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.13(d, 1H, J=1.68 Hz), 8.04 (d, 1H, J=8.80 Hz), 7.94 (d, 1H, J=7.88 Hz),7.33-7.78 (m, 16H), 3.99 (s, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with the triflate (100 mg,0.23 mmol), 3-cyanophenylboronic acid (45 mg, 0.30 mmol),water/acetonitrile (2 mL/6 ml), K₂CO₃ (17 mg, 0.12 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (11 mg, 0.023mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0mg, 0.009 mmol) was added and the solution was carefully degassed. Thereaction mixture was heated to 80° C. and stirred for 4 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (30 mL)and washed with saturated NaHCO₃ (10 mL), brine (10 mL), dried overNa₂SO₄. The organic layer was concentrated with a rotavapor and purifiedon silica gel. Elution with 5% EtOAc/hexanes afforded the desiredcompound (82 mg, 92%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.13(d, 1H, J=1.72 Hz), 8.10 (d, 1H, J=8.84 Hz), 8.04 (s, 1H), 7.98 (d, 2H,J=8.12 Hz), 7.78 (s, 1H), 7.46-7.74 (m, 12H), 7.40 (m, 1H).

Example 71 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer under N₂ wascharged with the starting material amine (20 mg, 0.05 mmol), MeOH (2mL), formaldehyde (37% in water, 44 μl, 0.5 mmol), and zinc chloride (4mg, 0.025 mmol) at room temperature. Sodium cyanoborohydride (4 mg,0.05) was added. After being stirred at room temperature for 12 h, thereaction mixture was treated with 0.1 N NaOH (1 mL). After most ofmethanol was evaporated under reduced pressure, the aqueous solution wasextracted with ethyl acetate (20 mL×2). The combined extracts werewashed with water and brine, dried over Na₂SO₄, concentrated with arotavapor and purified on silica gel. Elution with 5% MeOH/CHCl₃afforded the desired compound (20 mg, 91%) as a white foam solid. ¹H NMR(CDCl₃, 400 MHz) δ 8.17 (d, 1H, J=1.36 Hz), 8.06 (d, 1H, J=8.80 Hz),7.96 (d, 1H, J=8.12 Hz), 7.34-7.80 (m, 16H), 3.56 (s, 2H), 2.33 (s, 6H).

Example 72 Preparation of Compound

A solution of the compound of Example 71 dimethylamine (15 mg, 0.04mmol) in iodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 60°C. overnight. After cooled to room temperature, the reaction mixture wasadded Et₂O. The solid was collected by filtration to afford the desiredcompound (10 mg, 50%) as a light yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ8.15 (d, 1H, J=1.36 Hz), 8.04 (d, 1H, J=8.92 Hz), 8.00 (s, 1H), 7.96 (d,1H, J=7.96 Hz), 7.85 (d, 1H, J=7.96 Hz), 7.64-7.74 (m, 6H), 7.50-7.60(m, 3H), 7.43-7.52 (m, 4H), 7.33-7.38 (m, 1H), 5.14 (s, 2H), 3.44 (s,9H).

Example 73 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-fluorophenyl)naphthalene-6-yl trifluoromethanesulfonate (40 mg,0.11 mmol), 3-(dimethylamino)phenylboronic acid (30 mg, 0.18 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (30 mg, 0.27 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6 mg, 0.011mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0mg, 0.006 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 1 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (30 mL)and washed with saturated NaHCO₃ (10 mL), brine (10 mL), dried overNa₂SO₄. The organic layer was concentrated on a rotavapor and purifiedon silica gel. Elution with 5% EtOAc/hexanes afforded the desiredcompound (30 mg, 82%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.03(d, 1H, J=1.56 Hz), 7.80-7.86 (m, 2H), 7.64 (dd, 1H, J=1.88, 8.84 Hz),7.39-7.48 (m, 3H), 7.27-7.32 (m, 2H), 7.10-7.18 (m, 2H), 6.97-7.01 (m,2H), 6.71 (dd, 1H, J=2.56, 8.28 Hz), 2.30 (s, 6H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-bromonaphthalen-2-ol (100 mg, 0.45 mmol), 4-fluorophenylboronic acid(125 mg, 0.89 mmol), water/dioxane (2 mL/6 ml), K₂CO₃ (124 mg, 0.90mmol). The resulting solution was degassed for 5 min, then Pd(PPh₃)₄ (26mg, 0.02 mmol) was added. The reaction mixture was warmed to 100° C. andstirred for 3 h. After cooled to room temperature, the reaction mixturewas diluted with EtOAc (30 mL) and washed with saturated NaHCO₃ (15 mL),brine (15 mL), dried over NaSO₄. The organic layer was concentrated inrotavapor and purified on silica gel. Elution with 10% EtOAc/hexanesafforded the desired compound (98 mg, 92%) as a white solid. ¹H NMR(CDCl₃, 400 MHz) δ 7.73 (d, 1H, J=9.16 Hz), 7.68 (d, 1H, J=8.24 Hz),7.38-7.48 (m, 3H), 7.12-7.26 (m, 5H), 7.04 (dd, 1H, J=2.6, 9.12 Hz),5.11 (s, 3H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with 5-(4-fluorophenyl)naphthalene-2-ol (98 mg,0.41 mmol), CH₂Cl₂ (10 mL), and triethylamine (0.15 ml, 1.1 mmol). Aftercooling to −70° C., triflic anhydride (0.1 ml, 0.59 mmol) was added viaa syringe. The resulting reaction mixture was stirred at −70→−30° C. for30 min. The reaction mixture was diluted with CH₂Cl₂ (30 mL) and washedwith saturated NaHCO₃ (10 ml), brine (10 mL), dried over Na₂SO₄,concentrated in rotavapor and purified on silica gel. Elution with 5%EtOAc/hexanes afforded the desired compound (133 mg, 88%) as colorlessoil. ¹H NMR (CDCl₃, 400 MHz) δ 7.85 (d, 1H, J=9.32 Hz), 7.81 (d, 1H,J=8.28 Hz), 7.74 (d, 1H, J=2.44 Hz), 7.55 (t, 1H, J=7.20 Hz), 7.42 (dd,1H, J=0.96, 6.12 Hz), 7.30-7.38 (m, 2H), 7.25 (dd, 1H, J=2.48, 9.32 Hz),7.13 (m, 2H).

Example 74 Preparation of Compound

A solution of the3-(1-(4-fluorophenyl)naphthalen-6-yl)-N,N-dimethylbenzenamine (30 mg,0.09 mmol) in iodomethane (1.0 mL) was stirred in a sealed 2-dram vialat 70° C. overnight. After cooled to room temperature, Et₂O was added tothe suspension. The solid was collected by filtration to afford thedesired compound (35 mg, 83%) as off white solid. ¹H NMR (DMSO, 400 MHz)δ 8.55 (s, 1H), 8.42 (s, 1H), 8.01-8.16 (m, 4H), 7.95 (d, 1H, J=8.88Hz), 7.85 (t, 1H, J=8.12 Hz), 7.73 (t, 1H, J=7.96 Hz), 7.60-7.65 (m,2H), 7.56 (d, 1H, J=7.00 Hz), 7.46 (t, 2H, J=8.76 Hz), 3.77 (s, 9H).

Example 75 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-fluorophenyl)naphthalene-6-yl trifluoromethanesulfonate (43 mg,0.12 mmol), 4-(dimethylamino)phenylboronic acid (30 mg, 0.18 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (30 mg, 0.27 mmol),2-dicyclohexylphosphino-2′,4′6′-triisopropylbiphenyl (6 mg, 0.011 mmol).The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2.0 mg,0.006 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 100° C. and stirred for 1 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (30 mL)and washed with saturated NaHCO₃ (10 mL), brine (10 mL), dried overNa₂SO₄. The organic layer was concentrated in rotavapor and purified onsilica gel. Elution with 5% EtOAc/hexanes afforded the desired compound(35 mg, 88%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 7.97 (d, 1H,J=1.48 Hz), 7.80 (t, 2H, J=8.20 Hz), 7.62 (dd, 1H, J=1.64, 8.84 Hz),7.57 (d, 2H, J=8.64), 7.38-7.45 (m, 3H), 7.27 (d, 1H, J=7.0 Hz),7.09-7.14 (m, 2H), 6.78 (d, 2H, J=8.7 Hz), 2.95 (s, 6H).

Example 76 Preparation of Compound

A solution of4-(1-(4-fluorophenyl)naphthalen-6-yl)-N,N-dimethylbenzenamine (35 mg,0.10 mmol) in iodomethane (1.0 mL) was stirred in a sealed 2-dram vialat 70° C. overnight. After cooled to room temperature, Et₂O was added tothe suspension. The solid was collected by filtration to afford thedesired compound (40 mg, 80%) as a light yellow solid. ¹H NMR (DMSO, 400MHz) δ 8.51 (s, 1H), 8.14-8.20 (m, 5H), 7.92-8.00 (m, 2H), 7.72 (t, 1H,J=7.20 Hz), 7.58-7.65 (m, 2H), 7.55 (d, 1H, J=7.04 Hz), 7.46 (t, 2H,J=8.84 Hz), 3.73 (s, 9H).

Example 77 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with3-(2-(3-(dimethylamino)phenyl)naphthalen-5-yl)phenyltrifluoromethanesulfonate (32 mg, 0.07 mmol), 4-tert-butylphenylboronicacid (15 mg, 0.08 mmol), water/acetonitrile (1 mL/3 ml), K₂CO₃ (20 mg,0.14 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (10mg, 0.02 mmol). The resulting solution was degassed for 5 min, thenPd(OAc)₂ (2.0 mg, 0.009 mmol) was added and the solution was carefullydegassed. The reaction mixture was warmed to 80° C. and stirred for 12h. After cooled to room temperature, the reaction mixture was dilutedwith EtOAc (50 mL) and washed with saturated NaHCO₃ (15 mL), brine (15mL), dried over Na₂SO₄, concentrated with a rotavapor and purified onsilica gel. Elution with 5% EtOAc/hexanes afforded the desired compound(15 mg, 48%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.03 (d, 1H,J=1.60 Hz 1H), 7.95 (d, 1H, J=8.80 Hz), 7.85 (d, 1H, J=8.08 Hz),7.38-7.69 (m, 11H), 7.28 (t, 1H, J=7.88 Hz), 6.97-7.01 (m, 2H), 6.70(dd, 1H, J=2.50, 8.24 Hz), 2.96 (s, 6H), 1.29 (s, 9H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-bromonaphthalen-2-ol (500 mg, 2.24 mmol), 3-(benzyloxy)phenylboronicacid (1.02 g, 4.48 mmol), water/dioxane (4 mL/12 ml), K₂CO₃ (618 mg,4.48 mmol). The resulting solution was degassed for 5 min, thenPd(PPh₃)₄ (129 mg, 0.11 mmol) was added. The reaction mixture was warmedto 100° C. and stirred for 12 h. After cooled to room temperature, thereaction mixture was diluted with EtOAc (60 mL) and washed withsaturated NaHCO₃ (20 mL), brine (20 mL), dried over Na₂SO₄, concentratedin rotavapor and purified on silica gel. Elution with 10% EtOAc/hexanesafforded the desired compound (371 mg, 51%) as a white solid. ¹H NMR(CDCl₃, 400 MHz) δ 7.71 (d, 1H, J=9.12 Hz), 7.61 (d, 1H, J=8.20 Hz),7.12-7.40 (m, 9H), 7.69-7.02 (m, 4H), 5.04 (s, 2H), 4.96 (s, 1H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with 5-(3-(benzyloxy)phenyl)naphthalene-2-ol (371mg, 1.14 mmol), CH₂Cl₂ (10 mL), and triethylamine (0.32 ml, 2.28 mmol).After cooling to −70° C., triflic anhydride (0.21 ml, 1.25 mmol) wasadded via a syringe. The resulting reaction mixture was stirred at−70→−30° C. for 30 min. The reaction mixture was diluted with CH₂Cl₂ (30mL) and washed with saturated NaHCO₃ (10 ml), brine (10 mL), dried overNa₂SO₄, concentrated with a rotavapor and purified on silica gel.Elution with 5% EtOAc/hexanes afforded the desired compound (480 mg,92%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 7.86 (d, 1H, J=9.28Hz), 7.80 (d, 1H, J=7.96 Hz), 7.72 (d, 1H, J=2.52 Hz), 7.54 (t, 1H,J=8.04 Hz), 7.18-7.43 (m, 9H), 7.97-7.00 (m, 2H), 5.06 (s, 2H).

c. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(3-(benzyloxy)phenyl)naphthalen-6-yl trifluoromethanesulfonate (195mg, 0.12 mmol), 4-(dimethylamino)phenylboronic acid (84 mg, 0.51 mmol),water/acetonitrile (1 mL/4 ml), K₂CO₃ (200 mg, 1.44 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (20 mg, 0.04mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (5.0mg, 0.02 mmol) was added and the solution was carefully degassed. Thereaction mixture was heated to 100° C. and stirred for 1 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (50 mL)and washed with saturated NaHCO₃ (15 mL), brine (15 mL), dried overNa₂SO₄, concentrated on a rotavapor and purified on silica gel. Elutionwith 5% EtOAc/hexanes afforded the desired compound (168 mg, 92%) as awhite solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.02 (s, 1H), 7.87 (d, 1H, J=8.92Hz), 7.84 (d, 1H, J=8.52 Hz), 7.61 (d, 1H, J=8.76 Hz), 7.24-7.48 (m,9H), 6.99-7.08 (m, 5H), 6.71 (1H, d, J=8.16 Hz), 5.06 (s, 2H), 2.97 (s,6H).

d. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer was chargedwith 3-(1-(3-(benzyloxy)phenyl)naphthalen-6-yl)-N,N-dimethylbenzenamine(168 mg, 0.26 mmol), MeOH (15 mL), and Pd/C (10%, 20 mg). The reactionflask was sealed with septum and purge with N₂ three times; H₂ threetimes. The reaction mixture was stirred at room temperature under H₂balloon for 12 h. TLC showed the starting material was consumed. Thereaction mixture was passed through a pad of Celite and washed withMeOH. The filtrate was concentrated to afford the crude desired compoundas a grey solid. The crude product was used in next step without furtherpurification.

e. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with3-(2-(3-(dimethylamino)phenyl)naphthalen-5-yl)phenol (140 mg, 0.41mmol), CH₂Cl₂ (5 mL), and triethylamine (0.11 ml, 0.82 mmol). Aftercooling to −70° C., triflic anhydride (76 μl, 0.45 mmol) was added via asyringe. The resulting reaction mixture was stirred at −70° C. for 30min. The reaction mixture was diluted with CH₂Cl₂ (30 mL) and washedwith saturated NaHCO₃ (10 ml), brine (10 mL), dried over Na₂SO₄,concentrated and purified on silica gel. Elution with 5% EtOAc/hexanesafforded the desired compound (140 mg, 72%) as colorless oil. ¹H NMR(CDCl₃, 400 MHz) δ 8.04 (d, 1H, J=1.64 Hz), 7.89 (d, 1H, J=8.20 Hz),7.79 (d, 1H, J=8.76 Hz), 7.68 (dd, 1H, J=1.84, 8.80 Hz), 7.46-7.55 (m,3H), 7.26-7.38 (m, 4H), 7.67-7.00 (m, 2H), 6.72 (dd, 1H, d, J=2.56, 8.28Hz), 2.97 (s, 6H).

Example 78 Preparation of Compound

A solution of the compound of Example 77 (12 mg, 0.03 mmol) iniodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 80° C.overnight. After cooled to room temperature, Et₂O was added to thesuspension. The solid was collected by filtration to afford the desiredcompound (8.8 mg, 55%) as a light yellow solid. ¹H NMR (CDCl₃, 400 MHz)δ 8.28 (s, 1H), 8.00-8.06 (m, 3H), 7.80-7.83 (m, 2H), 7.38-7.67 (m,12H), 4.05 (s, 9H), 1.29 (s, 9H).

Example 79 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with3-(2-(3-(dimethylamino)phenyl)naphthalen-5-yl)phenyltrifluoromethanesulfonate (32 mg, 0.07 mmol),4-(trifluoromethyl)phenylboronic acid (26 mg, 0.14 mmol),water/acetonitrile (1 mL/3 ml), K₂CO₃ (20 mg, 0.14 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (10 mg, 0.03mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (2mg, 0.008 mmol) was added and the solution was carefully degassed. Thereaction mixture was warmed to 80° C. and stirred for 4 h. After cooledto room temperature, the reaction mixture was diluted with EtOAc (30 mL)and washed with saturated NaHCO₃ (10 mL), brine (10 mL), dried overNa₂SO₄, concentrated in rotavapor and purified on silica gel. Elutionwith 5% EtOAc/hexanes afforded the desired compound (22 mg, 69%) as awhite solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.04 (s, 1H), 7.87-7.92 (m, 2H),7.60-7.77 (m, 7H), 7.47-7.56 (m, 3H), 7.40 (d, 1H, J=6.96 Hz), 7.28 (t,1H, J=7.92 Hz), 6.98-7.01 (m, 2H), 6.72 (dd, 1H, J=2.48, 8.12 Hz), 2.96(s, 6H).

Example 80 Preparation of Compound

A solution of the compound of Example 79 (22 mg, 0.05 mmol) iniodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 80° C.overnight. After cooled to room temperature, Et₂O was added to thesuspension. The solid was collected by filtration to afford the desiredcompound (20 mg, 69%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.47(d, 1H, J=1.88 Hz), 8.28-8.29 (m, 1H), 8.22 (d, 1H, J=8.16 Hz), 8.18 (d,1H, J=8.84 Hz), 7.96-8.02 (m, 2H), 7.78-7.89 (m, 8H), 7.70-7.75 (m, 2H),7.63-7.67 (m, 2H), 4.24 (s, 9H).

Example 81 Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with the starting materialthe triflate (16 mg, 0.03 mmol), 3-(dimethylamino)phenylboronic acid (7mg, 0.45 mmol), water/acetonitrile (1 mL/3 ml), K₂CO₃ (20 mg, 0.14mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6 mg,0.012 mmol). The resulting solution was degassed for 5 min, thenPd(OAc)₂ (2.0 mg, 0.009 mmol) was added and the solution was carefullydegassed. The reaction mixture was warmed to 100° C. and stirred for 1h. After cooled to room temperature, the reaction mixture was dilutedwith EtOAc (30 mL) and washed with saturated NaHCO₃ (10 mL), brine (10mL), dried over Na₂SO₄. The organic layer was concentrated in rotavaporand purified on silica gel. Elution with 5% EtOAc/hexanes afforded amixture (10 mg, ˜90% pure) of the desired compound and some impurity.The mixture was used in next step without further purification.

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with 5-bromonaphthalen-2-ol(40 mg, 0.18 mmol), 3,5-di(4-fluorophenyl)phenylboronic acid (67 mg,0.22 mmol), water/dioxane (1 mL/3 ml), K₂CO₃ (50 mg, 0.36 mmol). Theresulting solution was degassed for 5 min, then Pd(PPh₃)₄ (10 mg, 0.009mmol) was added. The reaction mixture was heated to 90° C. and stirredfor 12 h. After cooled to room temperature, the reaction mixture wasdiluted with EtOAc (60 mL) and washed with saturated NaHCO₃ (20 mL),brine (20 mL), dried over Na₂SO₄, concentrated in rotavapor and purifiedon silica gel. Elution with 10% EtOAc/hexanes afforded a mixture of thedesired compound and some impurity (80 mg) as a white solid. The crudeproduct was used in next step without further purification.

b. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with the starting material phenol (80 mg, ˜0.20mmol), CH₂Cl₂ (5 mL), and triethylamine (56 μl, 0.40 mmol). Aftercooling to −70° C., triflic anhydride (40 μl, 0.24 mmol) was added via asyringe. The resulting reaction mixture was stirred at −70° C. for 30min, then room temperature for 1 h. The reaction mixture was dilutedwith CH₂Cl₂ (30 mL) and washed with saturated NaHCO₃ (10 ml), brine (10mL), dried over Na₂SO₄, concentrated, and purified on silica gel.Elution with 5% EtOAc/hexanes afforded the desired compound (16 mg) as awhite solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.00 (d, 1H, J=9.32 Hz), 7.86 (d,1H, J=8.08 Hz), 7.72 (s, 1H), 7.52-7.61 (m, 8H), 7.27 (dd, 1H, J=2.48,9.32 Hz), 7.07-7.11 (m, 4H).

Example 82 Preparation of Compound

A solution of the compound of Example 80 (10 mg, ˜0.02 mmol) iniodomethane (1.0 mL) was stirred in a sealed 2-dram vial at 80° C.overnight. After cooled to room temperature, Et₂O was added to thesuspension. The solid was collected by filtration to afford the desiredcompound (6 mg) as a light yellow solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.30(s, 1H), 8.04-8.11 (m, 3H), 7.78-7.84 (m, 2H), 7.49-7.72 (m, 11H),7.07-7.11 (m, 4H), 4.06 (s, 9H).

Example 83 Preparation of Compound

A 2-dram vial was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-(bromomethyl)benzoate (50 mg,0.1 mmol), acetonitrile (3 mL), methanamine (2 M in THF, 0.3 mL). Thesealed vial was stirred at room temperature for 15 min. The reactionmixture was diluted with EtOAc (30 mL), washed with saturated NaHCO₃ (10mL), brine (10 mL), dried over Na₂SO₄, concentrated on a rotavapor andpurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl/ammonium hydroxide) afforded the desired compound (40 mg, 86%)as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.27 (d, 1H, J=1.08 Hz),8.01-8.05 (m, 2H), 7.97 (s, 1H), 7.90 (d, 1H, J=8.04 Hz), 7.44-7.61 (m,8H), 3.97 (s, 3H), 3.44 (s, 2H), 2.20 (s, 6H), 1.45 (s, 9H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-t-butylphenyl)naphthalen-6-yl trifluoromethanesulfonate (500 mg,1.22 mmol), methyl3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (30 mg,1.45 mmol), water/acetonitrile (3 mL/9 ml), K₂CO₃ (337 mg, 2.44 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (30 mg, 0.061mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂(11.2 mg, 0.05 mmol) was added and the solution was carefully degassed.The reaction mixture was heated to 100° C. and stirred for 2 h. Aftercooled to room temperature, the reaction mixture was diluted with EtOAc(60 mL) and washed with saturated NaHCO₃ (20 mL), brine (20 mL), driedover Na₂SO₄. The organic layer was concentrated in rotavapor andpurified on silica gel. Elution with 5% EtOAc/hexanes afforded thedesired compound (466 mg, 93%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 8.02 (d, 1H, j=8.68 Hz), 7.99 (s, 1H), 7.94 (dd, 1H, J=1.32, 7.88 Hz),7.87 (d, 1H, J=8.12 Hz), 7.83 (d, 1H, J=1.68 Hz), 7.39-7.58 (m, 8H),3.95 (s, 3H), 2.36 (s, 3H), 1.42 (s, 9H).

b. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-methylbenzoate (466 mg, 1.14mmol), CCl₄ (10 mL), AIBN (19 mg, 0.11 mmol), and NBS (213 mg, 1.20mmol). The reaction mixture was degassed for 5 min then heated to 80° C.for 1 h. After additional NBS (50 mg) was added. The reaction mixturewas stirred for another 1 h. After cooled to room temperature, thereaction mixture was added hexanes (60 mL). The solid was removed byfiltration and the filtrate was concentrated on a rotavapor and purifiedon silica gel. Elution with 2% EtOAc/hexanes afforded the desiredcompound (395 mg, 71%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.26(d, 1H, J=1.64 Hz), 7.80-8.08 (m, 3H), 7.90 (d, 1H, J=8.16 Hz),7.43-7.61 (m, 8H), 4.52 (s, 2H), 3.97 (s, 3H), 1.42 (s, 9H).

Example 84 Preparation of Compound

A solution of methyl4-(1-(4-tert-butylphenyl)naphthalen-6-yl)-3-(dimethylaminomethyl)benzoate(10 mg, 0.21 mmol) in iodomethane (1.0 mL) in a sealed 2-dram vial wasstirred at 50° C. overnight. After cooled to room temperature, Et₂O wasadded to the reaction mixture. The solid was collected by filtration.After triturated with Et₂O and dried, there was obtained the desiredcompound (8 mg, 62%) as a white solid. ¹H NMR (MeOD, 400 MHz) δ 8.30 (d,1H, J=1.64 Hz), 8.19 (dd, 1H, J=1.72, 8.04 Hz), 8.99 (d, 1H, J=8.76 Hz),7.94 (d, 1H, J=1.64 Hz), 7.88 (d, 1H, J=8.28 Hz), 7.33-7.62 (m, 8H),4.77 (s, 2H), 3.89 (s, 3H), 2.74 (s, 9H), 1.32 (s, 9H).

Example 85 Preparation of Compound

A 10-ml flask was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-((dimethylamino)methyl)benzoate(28 mg, 0.06 mmol), THF/H₂O (1 mL/0.5 mL), LiOH (26 mg, 0.6 mmol). Afterstirred at 60° C. for 12 h, the reaction mixture was cooled to roomtemperature and adjusted to pH=2 by adding 1 N HCl. The solid wascollected and washed with Et₂O to afford the desired compound (12 mg,41%) as a white solid. ¹H NMR (MeOD, 400 MHz) δ 8.30 (d, 1H, J=1.32 Hz),8.12 (dd, 1H, J=1.60, 8.00 Hz), 7.96 (d, 1H, J=8.68 Hz), 7.80-7.89 (m,1H), 7.33-7.56 (m, 8H), 4.41 (s, 2H), 2.53 (s, 6H), 1.32 (s, 9H).

Example 86 Preparation of Compound

A 2-dram vial was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-(bromomethyl)benzoate (50 mg,0.1 mmol), acetonitrile (3 mL), methanamine (2 M in THF, 0.5 mL)). Thesealed vial was stirred at room temperature for 30 min. The reactionmixture was diluted with EtOAc (30 mL), washed with saturated NaHCO₃ (10mL), brine (10 mL), dried over Na₂SO₄, concentrated with a rotavapor andpurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (30 mg,67%) as colorless oil. ¹H NMR (CDCl₃, 400 MHz) δ 8.28 (s, 1H), 8.03-8.07(m, 2H), 7.90-7.94 (m, 2H), 7.44-7.62 (m, 8H), 3.97 (s, 3H), 3.87 (s,2H), 2.38 (s, 3H), 1.44 (s, 9H).

Example 87 Preparation of Compound

A 10-ml flask was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-((methylamino)methyl)benzoate(25 mg, 0.06 mmol), THF/H₂O (1 mL/0.5 mL), LiOH (26 mg, 0.6 mmol). Afterstirred at 80° C. for 12 h, the reaction mixture was cooled to roomtemperature and adjusted to pH=2 by adding 1 N HCl. The solid wascollected and washed with Et₂O to afford the desired compound (8 mg,31%) as a white solid. ¹H NMR (MeOD, 400 MHz) δ 8.20 (s, 1H), 8.06 (dd,1H, J=1.56, 8.00 Hz), 7.94 (d, 1H, J=8.72 Hz), 7.85-7.87 (m, 2H),7.32-7.54 (m, 8H), 4.22 (s, 2H), 2.46 (s, 3H), 1.32 (s, 9H).

Example 88 Preparation of Compound

A 10-ml flask was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-(aminomethyl)benzoate (14 mg,0.03 mmol), THF/H₂O (1 mL/0.5 mL), LiOH (25 mg, 0.5 mmol). After stirredat 80° C. for 12 h, the reaction mixture was cooled to room temperatureand adjusted to pH=2 by adding 1 N HCl. The solid was collected andwashed with Et₂O to afford the desired compound (6 mg, 40%) as a whitesolid. ¹H NMR (MeOD, 400 MHz) δ 7.98 (d, 1H, J=1.48 Hz), 7.80-7.86 (m,4H), 7.44-7.49 (m, 3H), 7.32-7.36 (m, 4H), 7.22 (d, 1H, J=7.84 Hz), 3.71(s, 2H), 1.32 (s, 9H).

Example 89 Preparation of Compound

A 10-ml flask was added methyl4-(1-(4-tert-butylphenyl)naphthalen-6-yl)-3-(azidomethyl)benzoate (45mg, 0.1 mmol), THF/water (3 mL/0.3 mL), and triphenylphosphine polymerbound (˜3.0 mmol/g, 100 mg). The reaction mixture was stirred at roomtemperature for 12 h. The solid was removed by filtration and thefiltrate was dried over Na₂SO₄, concentrated in rotavapor and purifiedon silica gel. Elution with 50% EtOAc/hexanes afforded the desiredcompound (16 mg, 37%) as colorless oil. ¹H NMR (MeOD, 400 MHz) δ 8.15(s, 1H), 7.80-7.91 (m, 4H), 7.46-7.51 (m, 3H), 7.33-7.38 (m, 5H), 3.85(s, 3H), 3.77 (s, 2H), 1.32 (s, 9H). The requisite intermediate for thepreparation of this compound was prepared as follows.

a. Preparation of Compound

A 10-ml flask was added methyl4-(1-(4-t-butylphenyl)naphthalen-6-yl)-3-(bromomethyl)benzoate (50 mg,0.1 mmol), DMF (1 mL), sodium azide (13 mg, 0.2 mmol). After stirred atroom temperature for 12 h, the reaction mixture was diluted with EtOAc(30 mL), washed with 10% LiCl (10×2 mL), dried over Na₂SO₄, concentratedwith a rotavapor and purified on silica gel. Elution with 10%EtOAc/hexanes afforded the desired compound (45 mg, 97%) as a whitesolid. ¹H NMR (CDCl₃, 400 MHz) δ 8.11 (d, 1H, J=1.52 Hz), 8.02 (dd, 1H,J=1.72, 7.96 Hz), 7.98 (d, 1H, J=8.72 Hz), 7.80-7.82 (m, 2H), 7.38-7.53(m, 7H), 7.33 (dd, 1H, J=1.80, 8.72 Hz), 4.32 (s, 2H), 3.90 (s, 3H),1.35 (s, 9H).

Example 90 Preparation of Compound

1-([1,1′-Biphenyl]-4-yl)-6-(2-nitrophenyl)naphthalene (64 mg, 0.159 mM)was dissolved with 1 mL of hydrazine in 20 mL of ethanol. 15 mg Pd/C wasadded and mixture was allowed to stir at 85° C. for 2.5 hours. Crudemixture was then diluted with 40 mL of EtOAc and filtered through alayer Celite and silica. Filtrate was then subjected to drying withNa₂SO₄ followed by in vacuo concentration. Crude was subjected to flashchromatography in which 20% EtOAc/hexanes eluted product (58 mg, 99%) ¹HNMR (400 MHz, CDCl₃) d=3.72 (s, 2H), 6.69 (1, J=7.96 1H), 6.78 (t,J=7.48 1H), 7.10 (t, J=8.08, 1H), 7.13 (d, J=7.13 Hz, 1H), 7.28 (t,J=7.56, 1H), 7.37 (t, J=5.76 Hz, 3H), 7.45-7.50 (m, 4H), 7.57-763 (m,4H), 7.78 (d, J=8.04 Hz, 1H), 7.88 (s, 1H), 7.96 (d, J=8.72, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

5-([1,1′-Biphenyl]-4-yl)naphthalen-2-yl trifluoromethanesulfonate (308mg, 0.719 mM) was combined with (2-nitrophenyl)boronic acid (240 mg, 1.4mM), K₂CO₃ (248 mg, 1.8 mM), and XPhos (34 mg, 0.072 mM). All this wasdissolved in a solution consisting of 9 mL of acetonitrile and 3 mL H₂O.The mixture was then brought to 100° C. Pd(OAc)₂ (10 mg, 0.046 mM) wasthen added and mixture was allowed to stir overnight. After cooling toroom temperature, crude reaction mixture was diluted with 50 mL of EtOAcand then filtered through a plug of Celite and silica. Contents werethen dried using Na₂SO₄ followed by vacuum concentration. Final product(103 mg, 36% yield) was afforded as a yellow solid using flashchromatography (10% EtOAc/hexanes). ¹H NMR (400 MHz, CDCl₃) d=7.25-7.30(m, 1H) 7.36-7.43 (m, 5H), 7.43-7.55 (m, 5H), 7.57-7.66 (m, 4H),7.75-7.82 (m, 3H), 7.93 (d, J=8.76 Hz, 1H)

b. Preparation of Compound

5-([1,1′-Biphenyl]-4-yl)naphthalen-2-ol (249 mg, 0.84 mM) was dissolvedwith triethylamine (0.23 mL, 1.68 mM) in 12 mL of anhydrousdichloromethane. Mixture was then cooled down to −78° C. After cooling,triflic anhydride (0.212 mL, 1.26 mM) was added drop wise to themixture. After stirring for one hour, mixture was diluted with 50 mL ofdichloromethane and washed with saturated NaHCO₃ followed by a washingwith brine. The organic layer was dried using Na₂SO₄ and thenconcentrated in vacuo. Crude product was then subjected to flashchromatography in which purified product eluted with 5% EtOAc/hexanes.309 mg of product (89% yield) was afforded as a white solid. ¹H NMR (400MHz, CDCl₃) d=7.30 (dd, J=9.32 Hz, J=2.56 Hz, 1H) 7.39 (t, J=7.2 Hz,1H), 7.48 (t, J=7.48 Hz, 2H), 7.52-7.55 (m, 3H), 7.63 (t, J=7.28 Hz,1H), 7.68 (d, J=7.28 Hz, 2H), 7.74 (d, J=8.08 Hz, 2H), 7.81 (dd, J=2.52Hz, 1H), 7.88 (d, J=8.16 Hz, 1H), 8.06 (d, J=9.32 Hz, 1H).

c. Preparation of Compound

5-Bromo-2-naphthol (201 mg, 0.91 mM) was combined with[1,1′-biphenyl]-4-ylboronic acid (360 mg, 1.82 mM), K₂CO₃ (314 mg, 2.28mM), and XPhos (43 mg, 0.091 mM). All this was dissolved in a solutionconsisting of 6 mL of acetonitrile and 2 mL H₂O. The mixture was thenbrought to 100° C. Pd(OAc)₂ (10 mg, 0.046 mM) was then added and mixturewas allowed to stir for 4.5 hours. After cooling to room temperature,crude reaction mixture was diluted with 50 mL of EtOAc and then filteredthrough a plug containing Celite and silica. The filtrate was then driedusing Na₂SO₄ followed by vacuum concentration. Final product wasisolated using flash chromatography (10% EtOAc/hexanes). 249 mg of5-([1,1′-biphenyl]-4-yl)naphthalen-2-ol as a white solid was afforded(93% yield). ¹H NMR (400 MHz, CDCl₃) d=5.4 (s, 1H), 7.1 (dd, J=2.5 Hz,J=9.12 Hz, 1H), 7.26 (d, J=2.48 Hz, 1H), 7.35 (d, J=7.04, 1H), 7.39-7.45(m, 1H), 7.53 (t, J=7.28 Hz, 3H), 7.60 (d, J=7.92 Hz, 2H), 7.74 (t,J=8.20 Hz, 5H), 7.92 (d, J=9.12 Hz, 1H)

Example 91 Preparation of Compound

2-(5-([1,1′-Biphenyl]-4-yl)naphthalen-2-yl)aniline (54 mg, 0.145 mM) wasdissolved with NaBH₃CN (29 mg, 0.465 mM) in 5 mL of CH₃CN. Several dropsof acetic acid were added to lower the pH to 6. After the desired pH wasachieved, 1 mL of formaldehyde was added and the mixture was allowed tostir overnight at room temperature. The next day, TLC revealed that thereaction mixture contained a considerable amount of the monomethylatedproduct. An additional 15 mg of NaBH₃CN was then added and after 4 hoursof stirring, the monomethylated product had fully converted to thedesired dimethylated compound. Product was extracted by diluting thereaction mixture with dichloromethane (50 mL) and washing with NaHCO₃and Brine. The organic layer was then dried with Na₂SO₄ followed by invacuo concentration. Crude was subjected to flash chromatography inwhich 10% EtOAc/hexanes eluted 23 mg of product (40% yield) as a whitesolid. ¹H NMR (400 MHz, CDCl₃) d=2.48 (s, 6H), 6.97-7.00 (m, 2H),7.20-7.31 (m, 3H), 7.37-7.47 (m, 4H), 7.55 (d, J=8 Hz, 2H), 760-7.66 (m,4H), 7.71 (dd, J=8.8 Hz, J=1.6 Hz, 1H), 7.81 (d, J=8.08 Hz, 1H), 7.91(d, J=8.84 Hz, 1H), 7.95 (s, 1H)

Example 92 Preparation of Compound

5-([1,1′-Biphenyl]-4-yl)naphthalen-2-yl trifluoromethanesulfonate (24mg, 0.056 mM) was combined with (3-(dimethylamino)phenyl)boronic acid(18.5 mg, 0.112 mM), K₂CO₃ (3 mg, 0.18 mM), and XPhos (3 mg, 0.006 mM).All this was dissolved in a solution consisting of 6 mL of acetonitrileand 2 mL H₂O. The mixture was then brought to 100° C. Pd(OAc)₂ (10 mg,0.046 mM) was then added and mixture was allowed to stir for 1.5 hours.After cooling to room temperature, crude reaction mixture was dilutedwith 50 mL of EtOAc and then filtered through a plug containing Celiteand silica gel. Contents were then dried using Na₂SO₄ followed by vacuumconcentration. Final product (5.4 mg, 24% yield) was afforded as a whitesolid using flash chromatography (10% EtOAc/hexanes). ¹H NMR (400 MHz,CDCl₃) d=3.03 (s, 6H), 6.78 (dd, J=2.32 Hz, J=8.28 Hz, 1H), 7.04-7.10(m, 1H), 7.33-7.41 (m, 2H), 7.45-7.52 (m, 3H), 7.56 (t, J=7.20 Hz, 2H),7.61 (d, J=8.20 Hz, 2H), 7.68-7.75 (m, 5H), 7.93 (d, J=8.16 Hz, 1H),8.04 (d, J=8.84 Hz, 1H), 8.11 (d, J=1.72 Hz, 1H)

Example 93 Preparation of Compound

3-(5-([1,1′-biphenyl]-4-yl)naphthalen-2-yl)-N,N-dimethylaniline wasdissolved in 4 mL of iodomethane and heated in a sealed tube at 100° C.for 24 hours. Unreacted Iodomethane was evaporated and crude product waswashed three times with ether to remove any unreacted starting material.The result was 2.8 mg of product (39% yield) as a beige powder. ¹H NMR(400 MHz, CDCl₃) d=4.09 (s, 9H), 7.39 (t, 7.32 Hz, 1H), 7.49 (t, J=7.4,2H), 7.53-7.65 (m, 4H), 7.67-7.78 (m, 6H), 7.82-7.83 (m, 1H), 7.93 (d,J=7.52 Hz, 1H), 8.06 (d, J=8.2 Hz, 1H), 8.08 (s, 1H), 8.13 (d, J=8.68Hz, 1H), 8.27 (s, 1H)

Example 94 Preparation of Compound

5-([1,1′-Biphenyl]-4-yl)naphthalen-2-yl trifluoromethanesulfonate (31mg, 0.072 mM) was combined with (4-(dimethylamino)phenyl)boronic acid(25 mg, 0.145 mM), K₂CO₃ (25 mg, 0.18 mM), and XPhos (4 mg, 0.007 mM).All this was dissolved in a solution consisting of 5 mL of acetonitrileand 3 mL H₂O. The mixture was then brought to 100° C. Pd(OAc)₂ (5 mg,0.22 mM) was then added and mixture was allowed to stir overnight. Aftercooling to room temperature, crude reaction mixture was diluted with 50mL of EtOAc and then filtered through a plug containing Celite andsilica gel. Contents were then dried using Na₂SO₄ followed by vacuumconcentration. Final product (18 mg, 62% yield) was afforded as a whitesolid using flash chromatography (10% EtOAc/hexanes). ¹H NMR (400 MHz,CDCl₃) d=2.94 (s, 6H), 6.78 (d, J=Hz, 2H), 7.28-7.36 (m, 2H), 7.39-7.48(m, 3H), 7.53 (m, 2H), 7.58 (m, 2H), 7.60-7.68 (m, 5H), 7.81 (d, J=8.20Hz, 1H), 7.92 (d, J=8.84 Hz, 1H), 7.98 (d, J=1.76 Hz, 1H)

Example 95 Preparation of Compound

4-(5-([1,1′-Biphenyl]-4-yl)naphthalen-2-yl)-N,N-dimethylaniline wasdissolved in 4 mL of iodomethane and heated in a sealed tube at 100° C.for 24 hours. Unreacted Iodomethane was evaporated and the crudereaction mixture was washed three times with ether to remove anyunreacted starting material. The result was 7 mg of product (37% yield)as a beige powder. ¹H NMR (400 MHz, CDCl₃) d=4.03 (s, 9H), 7.32 (t,J=7.4 Hz, 1H), 7.40-7.46 (m, 3H), 7.52 (t, J=6.52 Hz, 3H), 7.55-7.59 (m,2H), 7.63 (d, J=7.36 Hz, 2H), 7.68 (d, J=8.08 Hz, 2H), 7.89-7.87 (m,3H), 8.01 (s, 1H), 8.03-8.05 (m, 2H)

Example 96 Preparation of Compound

5-(4-(Trifluoromethyl)phenyl)naphthalen-2-yl trifluoromethanesulfonate(98 mg, 0.233 mM) was combined with (3-(dimethylamino)phenyl)boronicacid (77 mg, 0.466 mM), K₂CO₃ (81 mg, 0.583 mM), and XPhos (11 mg,0.0233 mM). All this was dissolved in a solution consisting of 5 mL ofacetonitrile and 3 mL H₂O. The mixture was then brought to 100° C.Pd(OAc)₂ (5 mg, 0.222 mM) was then added and mixture was allowed to stirfor 24 hours. After cooling to room temperature, crude reaction mixturewas diluted with 50 mL of EtOAc and then filtered through a plugcontaining Celite and silica gel. Contents were then dried using Na₂SO₄followed by vacuum concentration. Final product (74 mg, 81% yield) wasafforded as a white solid using flash chromatography (10%EtOAc/hexanes). ¹H NMR (400 MHz, CDCl₃) d=2.92 (s, 6H), 6.70 (dd, J=2.32Hz, J=8.28 Hz, 1H), 6.95 (m, 2H), 7.27 (m, 2H), 7.44 (t, J=7.28 Hz, 1H),7.54 (d, J=8.06 Hz, 2H), 7.63 (dd, J=1.9 Hz, J=8.84 Hz, 1H), 7.67 (d,J=8.16 Hz, 2H), 7.77 (d, J=8.8 Hz, 1H), 7.85 (d, J=8.2 Hz, 1H), 8.01 (s,1H)

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

5-(4-(trifluoromethyl)phenyl)naphthalen-2-ol (115 mg, 0.398 mM) wasdissolved with triethylamine (0.11 mL, 0.80 mM) in 8 mL of anhydrousdichloromethane. Mixture was then cooled to −78° C. Triflic anhydride(0.11 mL, 0.63 mM) was then added drop wise to the mixture. Afterstirring for one hour, mixture was then diluted with 50 mL ofdichloromethane and first washed with NaHCO₃ then organic layer waswashed brine. The organic layer was dried using Na₂SO₄ and then wasconcentrated in vacuo. Flash chromatography (5% EtOAc/hexanes) was usedto afford pure 5-(4-(trifluoromethyl)phenyl)naphthalen-2-yltrifluoromethanesulfonate (98 mg, 59% yield) as a white solid. ¹H NMR(400 MHz, CDCl₃) d=7.24 (dd, J=2.56 Hz, J=9.28 Hz, 1H), 7.40 (d, J=7 Hz,1H), 7.49 (d, J=8.32, 2H), 7.54 (t, J=7.36 Hz, 1H), 7.68 (d, J=8.24 Hz,2H), 7.74 (d, J=2.56 Hz, 1H), 7.81 (m, 2H)

b. Preparation of Compound

5-Bromo-2-naphthol (125 mg, 0.56 mM) was combined with(4-(trifluoromethyl)phenyl)boronic acid (213 mg, 1.12 mM) and K₂CO₃ (194mg, 1.4 mM). All this was dissolved in a solution consisting of 6 mL ofdioxane and 2 mL H₂O. This mixture was degassed and then Pd(PPh₃)₄ (42mg, 0.036 mM) was then added to the mixture. Mixture was allowed toreflux at 100° C. for 24 hours. Crude mixture was then diluted with 50mL of EtOAc and filtered through a plug containing Celite and silicagel. Filtrate was then dried using Na₂SO₄ followed by in vacuoconcentration. Flash chromatography was used to isolate product (115 mg,70% yield) which eluded from the column with 10% EtOAc/hexanes as awhite solid. ¹H NMR (400 MHz, CDCl₃) d=5.34 (s, 1H), 6.96 (dd, J=2.5 Hz,J=9.12 Hz, 1H), 7.11 (d, J=2.68 Hz, 1H), 7.13 (d, J=7.08, 1H), 7.36 (t,J=7.32 Hz, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.61 (t, J=8.88 Hz, 4H)

Example 97 Preparation of Compound

N,N-dimethyl-3-(5-(4-(trifluoromethyl)phenyl)naphthalen-2-yl)aniline wasdissolved in 5 mL of iodomethane and heated in a sealed tube at 100° C.for 3.5 hours. Unreacted iodomethane was evaporated and the crudereaction mixture was washed three times with ether to remove anyunreacted starting material. The result was 69.5 mg of product (80%yield) as a white powder. ¹H NMR (400 MHz, CDCl₃) d=4.17 (s, 9H), 7.49(d, J=7.04 Hz, 1H), 7.62 (m, 3H), 7.77 (m, 4H), 7.90-7.97 (m, 3H), 8.18(d, J=8.24 Hz, 1H), 8.27 (s, 1H), 8.45 (s, 1H).

Example 98 Preparation of Compound

1-(4-(t-Butyl)phenyl)-6-(4-nitrophenyl)naphthalene (75 mg, 0.197 mM) wasdissolved with 1 mL of hydrazine in 20 mL of ethanol. 15 mg Pd/C wasadded and mixture was allowed to stir at 85° C. overnight. The reactionmixture was then diluted with 50 mL of EtOAc and filtered through a plugof Celite and silica gel. Filtrate was then subjected to drying withNa₂SO₄ followed by in vacuo concentration. Crude was subjected to flashchromatography in which 20% EtOAc/hexanes eluted product as a whitesolid (quantitative yield). ¹H NMR (400 MHz, CDCl₃) d=1.34 (s, 9H), 3.69(s, 2H), 6.74 (d, J=8.16 Hz, 2H), 7.32 (d, J=7.04 Hz, 1H), 7.37-749 (m,7H), 7.58 (d, J=8.84 Hz, 1H), 7.79 (d, J=8.16 Hz, 1H), 7.92 (d, J=8.84Hz, 1H), 7.94 (s, 1H)

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

5-(4-(t-Butyl)phenyl)naphthalen-2-yl trifluoromethanesulfonate (105 mg,0.26 mM) was combined with (4-nitrophenyl)boronic acid (52 mg, 0.308mM), K₂CO₃ (88 mg, 0.643 mM), and XPhos (12 mg, 0.0257 mM). All this wasdissolved in a solution consisting of 9 mL of acetonitrile and 3 mL H₂O.The mixture was then brought to 100° C. Pd(OAc)₂ (8 mg, 0.0356 mM) wasthen added and mixture was allowed to stir overnight. After cooling toroom temperature, crude reaction mixture was diluted with 50 mL of EtOAcand then filtered through a plug containing Celite and silica gel.Contents were then dried using Na₂SO₄ followed by vacuum concentration.Final product (76 mg, 89% yield) was afforded as a yellow solid usingflash chromatography (15% EtOAc/hexanes). ¹H NMR (400 MHz, CDCl₃) d=1.45(s, 9H), 7.47-7.64 (m, 6H), 7.71 (dd, J=1.96 Hz, J=8.88 Hz 1H), 7.90 (d,J=8.88 Hz, 2H), 7.96 (d, J=8.12, 1H), 8.12 (d, J=8.96 Hz, 1H), 8.18 (s,1H), 8.38 (d, J=8.84 Hz, 2H)

b. Preparation of Compound

5-(4-(t-butyl)phenyl)naphthalen-2-yl trifluoromethanesulfonate wasprepared as described for Intermediate b of Example 59.

Example 99 Preparation of Compound

NaBH₃CN (30 mg, 0.482 mM) and 1.5 mL of formaldehyde were dissolved in10 mL of CH₃CN. Several drops of acetic acid was used to lower the pH to6. After desired pH was achieved,4-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)aniline (56 mg, 0.150 mM) wasadded to the solution and the mixture was allowed to stir overnight atroom temperature. Product was then extracted by diluting reactionmixture with dichloromethane (50 mL) and washing with NaHCO₃ and brine.The organic layer was then dried with Na₂SO₄ followed by in vacuoconcentration. Crude product was subjected to flash chromatography inwhich 10% EtOAc/hexanes eluted 56 mg of product (98% yield) as a whitesolid. ¹H NMR (400 MHz, CDCl₃) d=1.34 (s, 9H), 2.93 (s, 6H), 6.76-6.80(m, 2H), 7.29-7.32 (m, 1H), 7.37-7.45 (m, 5H), 7.55-7.61 (m, 3H),7.77-7.80 (m, 1H), 7.89-7.97 (m, 2H)

Example 100 Preparation of Compound

4-(5-(4-(t-Butyl)phenyl)naphthalen-2-yl)-N,N-dimethylaniline (26.2 mg,0.069 mM) was dissolved in 4 mL of iodomethane and heated in a sealedtube at 100° C. overnight. The next day, very little product hadprecipitated. The iodomethane was then evaporated and crude product wasdissolved in 2 mL of iodomethane and heated in a sealed tube for 8hours. After a reasonable amount of product had precipitated out, thecap of the sealed tube was removed and the iodomethane was allowed toevaporate. The crude reaction mixture was washed three times with etherto remove any unreacted starting material. The result was 12 mg ofproduct (33% yield) as a beige powder. ¹H NMR (400 MHz, CDCl₃) d=1.32(s, 9H), 3.64 (s, 9H), 7.31-7.36 (m, 3H), 7.42-7.53 (m, 5H), 7.68 (dd,J=8.8 Hz, J=1.92 Hz 1H), 7.79 (d, J=9.2 Hz, 1H), 7.86-7.92 (m, 3H), 8.17(s, 1H)

Example 101 Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with methyl3-(bromomethyl)-4-(5-(4-(tert-butyl)phenyl)naphthalen-2-yl)benzoate (30mg, 0.06 mmol), DMF (1 mL), K₂CO₃ (16 mg, 0.12 mmol), and1,3-bis(t-butoxycarbonyl)guanidine (20 mg, 0.07 mmol) The reactionmixture was stirred at room temperature for 12 h. The reaction mixturewas diluted with EtOAc (60 mL), washed with water (20 mL), 10% LiCl (20mL), brine (20 mL), dried over Na₂SO₄, concentrated, and purified onsilica gel. Elution with 5% EtOAc/hexanes afforded the desired compound(35 mg, 85%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 9.44 (broad s,1H), 9.26 (broad s, 1H), 8.00-8.05 (m, 2H), 7.90-7.91 (m, 2H), 7.85 (s,1H), 7.49-7.61 (m, 6H), 7.43 (d, 1H, J=7.92 Hz), 5.28 (s, 2H), 3.97 (s,3H), 1.50 (s, 9H), 1.45 (s, 9H), 1.26 (s, 9H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 10-mL vial was added methyl4-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-3-(((2,2,10,10-tetramethyl-4,8-dioxo-3,9-dioxa-5,7-diazaundecan-6-yl)amino)methyl)benzoate(35 mg, 0.05 mmol), CH₂Cl₂ (1 mL), and TFA (1 mL). The sealed vial wasstirred at 50° C. for 1 h. The solvent was removed and the residue waspurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₁/ammonium hydroxide) afforded the desired compound (16 mg,67%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.38 (broad s, 1H),7.92-7.98 (m, 3H), 7.77 (d, 1H, J=8.08 Hz), 7.71 (s, 1H), 7.41-7.52 (m,4H), 7.34-7.37 (m, 3H), 7.23 (dd, 1H, J=1.68, 8.80 Hz), 4.29 (d, 2H,J=5.40 Hz), 3.76 (s, 3H), 1.34 (s, 9H).

Example 102 Preparation of Compound

A 10-mL vial was addeddi-t-butyl(((2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-3,4-dimethoxybenzyl)amino)methylene)dicarbamate(35 mg, 0.05 mmol), CH₂Cl₂ (1 mL), and TFA (1 mL). The sealed vial wasstirred at 50° C. for 1 h. The solvent was removed and the residue waspurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (20 mg,80%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.34 (t, 1H, J=5.24Hz), 7.90-7.92 (m, 2H), 7.77 (d, 1H, J=8.12 Hz), 7.75 (dd, 1H, J=1.52,8.88 Hz), 7.41-7.45 (m, 3H), 7.33-7.37 (m, 3H), 6.83 (d, 1H, J=1.68 Hz),6.74 (d, 1H, J=1.76 Hz), 4.16 (d, 2H, J=5.32 Hz), 3.79 (s, 3H), 3.48 (s,3H), 1.33 (s, 9H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-(4-(t-butyl)phenyl)naphthalen-2-yl trifluoromethanesulfonate (1.0 g,2.45 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane)(746 mg, 2.94 mmol), dioxane (20 ml), KOAc (720 mg, 2.94 mmol). Theresulting solution was degassed for 5 min, then Pd(dppf)Cl₂ (70 mg, 0.09mmol) was added and the solution was carefully degassed. The reactionmixture was warmed to 80° C. and stirred for 1.5 h. After cooling toroom temperature, the reaction mixture was diluted with EtOAc (100 mL)and washed with saturated NaHCO₃ (30 mL), brine (30 mL), dried overNa₂SO₄. The organic layer was concentrated and purified on silica gel.Elution with 5% EtOAc/hexanes afforded the desired compound (836 mg,88%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.35 (s, 1H), 7.87 (d,1H, J=8.48 Hz), 7.81 (d, 1H, J=8.00 Hz), 7.70 (dd, 1H, J=1.20, 8.48 Hz),7.41-7.45 (m, 3H), 7.34-7.39 (m, 3H), 1.34 (s, 9H), 1.32 (s, 12H).

b. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(70 mg, 0.18 mmol), (2-bromo-3,4-dimethoxyphenyl)methanol (35 mg, 0.16mmol), water/dioxane (1 mL/4 ml), K₂CO₃ (50 mg, 0.36 mmol). Theresulting solution was degassed for 5 min, then Pd(PPh₃)₄ (5 mg, 0.004mmol) was added. The reaction mixture was warmed to 100° C. and stirredfor 2 h. After cooling to room temperature, the reaction mixture wasdiluted with EtOAc (50 mL) and washed with saturated NaHCO₃ (20 mL),brine (20 mL), dried over NaSO₄. The organic layer was concentrated andpurified on silica gel. Elution with 30% EtOAc/hexanes afforded thedesired compound (74 mg, 96%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 7.98 (d, 1H, =1.64 Hz), 7.92 (d, 1H, J=8.81 Hz), 7.81 (d, 1H, =8.20Hz), 7.60 (dd, 1H, J=1.80, 8.80 Hz), 7.36-7.49 (m, 6H), 6.99 (d, 1H,J=1.92 Hz), 6.94 (d, 1H, J=1.92 Hz), 4.65 (d, 2H, J=5.8 Hz), 3.88 (s,3H), 3.51 (s, 3H), 1.35 (s, 9H).

c. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer undernitrogen was charged with(2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-3,4-dimethoxyphenyl)methanol(74 mg, 0.18 mmol), CH₂Cl₂ (5 mL), and triethylamine (50 μl, 0.36 mmol).Methanesulfonyl chloride (20 μL, 0.27 mmol) was added via a syringe. Theresulting reaction mixture was stirred at room temperature overnight.The reaction mixture was diluted with CH₂Cl₂ (30 mL) and washed withsaturated NaHCO₃ (10 ml), brine (10 mL), dried over Na₂SO₄, andconcentrated to afford the desired compound (80 mg, 90%) as an off whitesolid. The crude product was used in next step without furtheridentification and purification.

d. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-3,4-dimethoxybenzylmethanesulfonate (40 mg, 0.08 mmol), DMF (1 mL), K₂CO₃ (22 mg, 0.16mmol), and 1,3-bis(t-butoxycarbonyl)guanidine (31 mg, 0.12 mmol) Thereaction mixture was stirred at 50° C. for 12 h. The reaction mixturewas diluted with EtOAc (40 mL), washed with water (10 mL), 10% LiCl (10mL), brine (10 mL), dried over Na₂SO₄, concentrated, and purified onsilica gel. Elution with 10% EtOAc/hexanes afforded the desired compound(35 mg, 66%) as a white solid, which was used in next step withoutfurther identification.

e. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with2-(5-(4-(tert-butyl)phenyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(75 mg, 0.19 mmol), methyl 2-(2-bromo-4,5-dimethoxyphenyl)acetate (36mg, 0.13 mmol), water/dioxane (1 mL/4 ml), K₂CO₃ (36 mg, 0.26 mmol). Theresulting solution was degassed for 5 min, then Pd(PPh₃)₄ (7 mg, 0.006mmol) was added. The reaction mixture was warmed to 100° C. and stirredfor 1 h. After cooling to room temperature, the reaction mixture wasdiluted with EtOAc (50 mL) and washed with saturated NaHCO₃ (20 mL),brine (20 mL), dried over NaSO₄. The organic layer was concentrated andpurified on silica gel. Elution with 10% EtOAc/hexanes afforded thedesired compound (48 mg, 89%) as a white solid. ¹H NMR (CDCl₃, 400 MHz)δ 7.92 (d, 1H, J=8.72 Hz), 7.76-7.78 (m, 2H), 7.45-7.50 (m, 3H),7.37-7.41 (m, 3H), 7.33 (dd, 1H, J=1.76, 8.68 Hz), 6.83 (s, 1H), 6.80(s, 1H), 3.87 (s, 3H), 3.81 (s, 3H), 3.57 (s, 3H), 3.51 (s, 2H), 1.35(s, 9H).

Example 103 Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with NH₄Cl (22 mg, 0.41mmol), toluene (2 mL), and cooled to 0° C. To this suspension, AlMe₃ (2M in hexanes, 0.20 mL, 0.41 mmol) was added drop wise over min thenwarmed to room temperature and stirred for 30 min. Methyl2-(2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-4,5-dimethoxyphenyl)acetate(40 mg, 0.08 mmol) was added as one portion and the resulting mixturewas heated to 80° C. and stirred for 12 h. After cooling to 0° C., MeOH(3 mL) was added over 5 min, then the reaction mixture was stirred atroom temperature for 1 h. The solid was removed by filtration and thefiltrate was concentrated and purified with silica gel. Elution withEtOAc afforded the desired compound (25 mg, 66%) as a white solid. ¹HNMR (CDCl₃, 400 MHz) δ 7.93 (d, 1H, J=8.68 Hz), 7.77 (d, 1H, J=8.20 Hz),7.74 (d, 1H, J=1.76 Hz, 7.44-7.51 (m, 3H), 7.38-7.40 (m, 3H), 7.31 (dd,1H, J=1.88, 8.68 Hz), 6.85 (s, 1H), 6.83 (s, 1H), 5.21 (broad s, 2H),3.88 (s, 3H), 3.82 (s, 3H), 3.47 (s, 2H), 1.35 (s, 9H).

Example 104 Preparation of Compound

A 20-mL vial was charged withdi-t-butyl(((2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)benzyl)amino)methylene)dicarbamate(330 mg, 0.54 mmol), CH₂Cl₂ (2 mL), and TFA (2 mL). The sealed vial wasstirred at 50° C. for 1 h. The solvent was removed and the residue waspurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (200 mg,91%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.29 (t, 1H, J=5.12Hz), 8.05 (d, 1H, J=8.64 Hz), 7.86 (d, 1H, J=8.12 Hz), 7.79 (d, 1H,J=1.56 Hz), 7.36-7.61 (m, 12H), 7.32 (dd, 1H, J=1.76, 8.80 Hz), 4.32 (d,2H, J=5.64 Hz), 1.44 (s, 9H). The requisite intermediate for thepreparation of this compound was prepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-(4-(t-butyl)phenyl)naphthalen-2-yl trifluoromethanesulfonate, preparedas described for Intermediate b of Example 59, (300 mg, 0.73 mmol),o-tolylboronic acid (150 mg, 1.10 mmol), water/acetonitrile (4 mL/16ml), K₂CO₃ (202 mg, 1.47 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (35 mg, 0.073mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (8.2mg, 0.04 mmol) was added and the solution was carefully degassed. Thereaction mixture was heated to 100° C. for 1 h. After cooling to roomtemperature, the reaction mixture was diluted with EtOAc (60 mL) andwashed with saturated NaHCO₃ (20 mL), brine (20 mL), dried over Na₂SO₄.The organic layer was concentrated and purified on silica gel. Elutionwith hexanes afforded the desired compound (240 mg, 93%) as a whitesolid. ¹H NMR (CDCl₃, 400 MHz) δ 7.92 (d, 1H, J=8.72 Hz), 7.79 (d, 1H,J=8.24 Hz), 7.76 (d, 1H, J=1.72 Hz), 7.34-7.48 (m, 7H), 7.18-7.27 (m,4H), 2.25 (s, 3H), 1.35 (s, 9H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-(4-(t-butyl)phenyl)-6-(o-tolyl)naphthalene (240 mg, 0.68 mmol), CCl₄(3 mL), AIBN (11 mg, 0.068 mmol), and NBS (134 mg, 0.75 mmol). Thereaction mixture was degassed for 5 min then heated to 85° C. for 1 h.After cooling to room temperature, the reaction mixture was addedhexanes (20 mL). The solid was removed by filtration and the filtratewas concentrated and purified with silica gel. Elution with hexanesafforded the desired compound (241 mg, 82%) as yellow oil. ¹H NMR(CDCl₃, 400 MHz) δ 7.97 (d, 1H, J=8.68 Hz), 7.91 (d, 1H, J=1.68 Hz),7.81 (d, 1H, J=8.16 Hz), 7.39-7.51 (m, 8H), 7.27-7.34 (m, 3H), 4.44 (s,2H), 1.35 (s, 9H).

c. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with6-(2-(bromomethyl)phenyl)-1-(4-(t-butyl)phenyl)naphthalene (240 mg, 0.56mmol), DMF (3 mL), K₂CO₃ (154 mg, 1.12 mmol), and1,3-bis(t-butoxycarbonyl)guanidine (290 mg, 1.12 mmol) The reactionmixture was stirred at 50° C. for 12 h. The reaction mixture was dilutedwith EtOAc (60 mL), washed with water (20 mL), 10% LiCl (20 mL), brine(20 mL), dried over Na₂SO₄, concentrated, and purified on silica gel.Elution with 5% EtOAc/hexanes afforded the desired compound (330 mg,97%) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 9.37 (broad s, 1H),9.23 (broad s, 1H), 7.92 (d, 1H, J=8.72 Hz), 7.78-7.81 (m, 2H),7.37-7.50 (m, 7H), 7.24-7.29 (m, 3H), 7.07 (d, 1H, J=7.84 Hz), 5.19(broad s, 2H), 1.41 (s, 9H), 1.35 (s, 9H), 1.12 (s, 9H).

Example 105 Preparation of Compound

A 10-mL vial was charged withdi-t-butyl(((2-(5-([1,1′-biphenyl]-3-yl)naphthalen-2-yl)benzyl)amino)methylene)dicarbamate(40 mg, 0.06 mmol), CH₂Cl₂ (1 mL), and TFA (1 mL). The sealed vial wasstirred at 50° C. for 1 h. The solvent was removed and the residue waspurified on silica gel. Elution with CH₂Cl₂ to (10/89/1:MeOH/CHCl₃/ammonium hydroxide) afforded the desired compound (25 mg, 92%in yield) as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.33 (broad s,1H), 8.00-8.06 (m, 2H), 7.90 (d, 1H, J=6.88 Hz), 7.34-7.74 (m, 16H),7.21 (broad s, 1H), 4.32 (broad s, 2H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

A 100-mL round bottom flask equipped with a magnetic stirrer, acondenser and a nitrogen in/outlet adapter was charged with5-([1,1′-biphenyl]-3-yl)naphthalen-2-yl trifluoromethanesulfonate (389mg, 0.91 mmol), o-tolylboronic acid (185 mg, 1.36 mmol),water/acetonitrile (4 mL/16 ml), K₂CO₃ (251 mg, 1.82 mmol),2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (43 mg, 0.09mmol). The resulting solution was degassed for 5 min, then Pd(OAc)₂ (10mg, 0.05 mmol) was added and the solution was carefully degassed. Thereaction mixture was heated to 100° C. for 1 h. After cooling to roomtemperature, the reaction mixture was diluted with EtOAc (60 mL) andwashed with saturated NaHCO₃ (20 mL), brine (20 mL), dried over Na₂SO₄.The organic layer was concentrated and purified on silica gel. Elutionwith hexanes afforded the desired compound (220 mg, 65% in yield) as awhite solid. ¹H NMR (CDCl₃, 400 MHz) δ 8.14 (d, 1H, J=1.72 Hz), 8.06 (d,1H, J=8.80 Hz), 7.96 (d, 1H, J=8.20 Hz), 7.80 (t, 1H, J=1.64 Hz),7.69-7.80 (m, 4H), 7.46-7.64 (m, 8H), 7.37-7.43 (m, 2H), 7.23 (d, 1H,J=7.52 Hz), 2.49 (s, 3H).

b. Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-([1,1′-biphenyl]-3-yl)-6-(o-tolyl)naphthalene (220 mg, 0.59 mmol),CCl₄ (4 mL), AIBN (10 mg, 0.06 mmol), and NBS (116 mg, 0.65 mmol). Thereaction mixture was degassed for 5 min then heated to 80° C. for 2 h.After cooling to room temperature, the reaction mixture was addedhexanes (20 mL). The solid was removed by filtration and the filtratewas concentrated and purified with silica gel. Elution with hexanesafforded the desired compound (240 mg, 90% in yield) as a solid. ¹H NMR(CDCl₃, 400 MHz) δ 8.00 (d, 1H, J=1.80 Hz), 7.93 (d, 1H, J=8.72 Hz),7.82 (d, 1H, J=7.80 Hz), 7.23-7.65 (m, 16H), 4.48 (s, 2H).

c. Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with1-([1,1′-biphenyl]-3-yl)-6-(2-(bromomethyl)phenyl)naphthalene (30 mg,0.07 mmol), DMF (1 mL), K₂CO₃ (17 mg, 0.13 mmol), and1,3-bis(tert-butoxycarbonyl)guanidine (26 mg, 0.1 mmol) The reactionmixture was stirred at 50° C. for 12 h. The reaction mixture was dilutedwith EtOAc (60 mL), washed with water (20 mL), 10% LiCl (20 mL), brine(20 mL), dried over Na₂SO₄, concentrated, and purified on silica gel.Elution with 5% EtOAc/hexanes afforded the desired compound (40 mg, 95%)as a white solid. ¹H NMR (CDCl₃, 400 MHz) δ 9.51 (broad s, 1H), 9.36(broad s, 1H), 8.12 (d, 1H, J=1.48 Hz), 8.05 (d, 1H, J=8.80 Hz), 7.95(d, 1H, J=8.12 Hz), 7.80 (t, 1H, J=1.64 Hz), 7.69-7.80 (m, 5H),7.37-7.65 (m, 9H), 7.29 (d, 1H, J=7.32 Hz), 5.30 (broad s, 2H), 1.50 (s,9H), 1.38 (s, 9H).

Example 106 Preparation of Compound

A 50-mL round bottom flask equipped with a magnetic stirrer, a condenserwas charged withN-(4-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-2,3-dimethoxyphenethyl)acetamide(30 mg, 0.06 mmol) and 50% HCl/MeOH (6 mL/6 mL). The reaction mixturewas warmed to 100° C. and stirred for 12 h. After cooling to roomtemperature, the solid was collected by filtration and washed with Et₂O.After drying, there was obtained the desired compound (20 mg, 67% inyield) as a white solid.

a.—Preparation of Compound

A 25-mL round bottom flask equipped with a magnetic stirrer, a condenserand a nitrogen in/outlet adapter was charged with2-(5-(4-(t-butyl)phenyl)naphthalen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(50 mg, 0.13 mmol), N-(4-bromo-2,3-dimethoxyphenethyl)acetamide (39 mg,0.13 mmol), water/dioxane (1 mL/4 ml), K₂CO₃ (36 mg, 0.26 mmol). Theresulting solution was degassed for 5 min, then Pd(PPh₃)₄ (7 mg, 0.006mmol) was added. The reaction mixture was warmed to 100° C. and stirredfor 2 h. After cooling to room temperature, the reaction mixture wasdiluted with EtOAc (50 mL) and washed with saturated NaHCO₃ (20 mL),brine (20 mL), dried over NaSO₄. The organic layer was concentrated andpurified on silica gel. Elution with 90% EtOAc/hexanes afforded thedesired compound (47 mg, 76% in yield) as a white solid. ¹H NMR (CDCl₃,400 MHz) δ 8.06 (d, 1H, J=1.60 Hz), 8.03 (d, 1H, J=8.88 Hz), 7.91 (d,1H, J=8.16 Hz), 7.64-7.72 (m, 2H), 7.46-7.58 (m, 5H), 7.18 (d, 1H,J=7.88 Hz), 7.03 (d, 1H, J=8.04 Hz), 3.99 (s, 3H), 3.64 (s, 3H), 3.37(m, 2H), 2.91 (t, 2H, J=6.56 Hz), 1.99 (s, 3H), 1.45 (s, 9H).

Example 107 Preparation of Compound

Prepared by General Method B (87% Yield); ¹H NMR (DMSO-d6, 400 MHz) δ:4.52 (s, 3H), 7.45-7.47 (m, 1H), 7.55 (t, J=8.0 Hz, 2H), 7.75 (d, J=8.0Hz, 2H), 7.81 (d, J=8.0 Hz, 2H), 7.99 (d, J=8.0 Hz, 2H), 8.20 (d, J=8.0Hz, 1H), 8.26 (d, J=8.0 Hz, 1H), 8.29 (m, 1H), 8.59 9d, J=8.0 Hz, 1H),8.85 (s, 1H), 10.04 (s, 1H).

Example 108 Preparation of Compound

Prepared by General Method A (85% Yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.40 (m, 2H), 7.52 (m, 3H), 7.60 (d, J=8.0 Hz, 2H), 7.69 (d, J=8.0 Hz,2H), 7.76 (m, 3H), 8.00 (d, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H), 8.97(d, J=4.0 Hz, 1H).

Example 109 Preparation of Compound

Prepared by General Method B (91% yield); ¹H NMR (CDCl₃, 400 MHz) δ:4.85 (s, 3H), 7.26-7.32 (m, 2H), 7.63-7.66 (m, 2H), 7.97-8.11 (m, 3H),8.37 (s, 1H), 8.75 (d, J=8.0 Hz, 1H), 10.88 (s, 1H).

Example 110 Preparation of Compound

Prepared by General Method A (88% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.22 (m, 2H), 7.47 (m. 2H), 7.66 (2H), 7.86 (d J=8.0 Hz, 1H), 8.05 (d,J=8.0 Hz, 1H), 8.46 (s, 1H), 9.26 (s, 1H).

Example 111 Preparation of Compound

Prepared by General Method A (88% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.39 (t, J=8.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 2H), 7.56 (d, J=8.0 Hz, 2H),7.70 (m, 4H), 7.75 (d, J=8.0 Hz, 2H), 8.0 (d, J=8.0 Hz, 1H), 8.51 (d,J=4.0 Hz, 1H), 9.32 (s, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

Prepared by General Method C (94% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.55-7.60 (m, 2H), 7.76 (t, J=8.0 Hz, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.42(d, J=8.0 Hz, 1H), 9.03 (m, 1H).

Example 112 Preparation of Compound

Prepared by General Method B (87% yield); ¹H NMR (CDCl₃, 400 MHz) δ:4.84 (s, 3H), 7.43 (m, 1H), 7.49-7.52 (m, 4H), 7.68 (d, J=4.0 Hz, 2H),7.78 (d, J=8.0 Hz, 2H), 8.04-8.12 (m, 2H), 8.34 (d, J=4.0 Hz, 1H), 8.53(bs, 1H), 8.72 (d, J=8.0 Hz, 1H), 10.9 (m, 1H).

Example 113 Preparation of Compound

Prepared by General Method A (84% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.41 (m, 1H), 7.48 (m, 3H), 7.70 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz,2H), 7.83 (d, J=8.0 Hz, 2H), 8.06 (m, 2H), 8.25 (t, 8.0 Hz, 2H), 8.97(m, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

Prepared by General Method C (94% yield) was used as isolated withoutfurther purification.

Example 114 Preparation of Compound

Prepared by General Method B (78% yield); ¹H NMR (DMSO-d6, 400 MHz) δ:4.68 (s, 3H), 7.45 (m, 1H), 7.53 (m, 2H), 7.79 (d, J=8.0 Hz, 2H), 7.92(d, J=8.0 Hz, 2H), 8.08 (d, J=8.0 Hz, 2H), 8.20 (m, 1H), 8.60 (d, J=12.0Hz, 1H), 8.72 (d, J=8.0 Hz, 1H), 8.89 (s, 1H), 9.29 (d, J=8.0 Hz, 1H),9.48 (d, J=8.0 Hz, 1H).

Example 115 Preparation of Compound

Prepared by General Method A (77% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.53-7.66 (m, 4H), 7.84 (d, J=8.0 Hz, 2H), 7.91 (d, J=8.0 Hz, 2H), 8.01(d, J=8.0 Hz, 2H), 8.06 (d, J=8.0 Hz, 2H), 8.36 (d, J=8.0 Hz, 1H), 8.57(s, 1H), 9.13 (m, 1H).

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

Prepared by General Method C (94% yield); ¹H NMR (CDCl₃, 400 MHz) δ:6.16 (d, J=8.0 Hz, 1H), 6.34 (m, 1H), 6.82 (d, J=8.0 Hz, 1H), 7.25 (m,1H), 7.39 (d, J=8.0 Hz, 1H), 7.76 (s, 1H).

Example 116 Preparation of Compound

Prepared by General Method B (83% yield); ¹H NMR (DMSO-d6, 400 MHz) δ:4.75 (s, 3H), 7.45 (m, 1H), 7.54 (t, J=8.0 Hz, 2H), 7.81 (d, J=8.0 Hz,2H), 7.95 (d, J=8.0 Hz, 2H), 8.17 (m, 3H), 8.5 (d, J=8.0 Hz, 1H), 8.58(d, J=8.0 Hz, 1H), 8.71 (s, 1H), 9.28 (d, J=8.0 Hz, 1H), 9.49 (d, J=8.0Hz, 1H).

Example 117 Preparation of Compound

Prepared by General Method A (84% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.30-7.41 (m, 4H), 7.52 (t, J=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 2H), 7.62(d, J=8.0 Hz, 2H), 7.63-7.74 (m, 3H), 8.11 (d, J=8.0 Hz, 1H), 8.23 (d,J=8.0 Hz, 1H), 8.88 (m, 1H)

The requisite intermediate for the preparation of this compound wasprepared as follows.

a. Preparation of Compound

Prepared by General Method C (92% yield); ¹H NMR (CDCl₃, 400 MHz) δ:7.52 (m, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.86 (d,J=8.0 Hz, 1H), 8.22 (d, J=8.0 Hz, 1H), 9.04 (m, 1H).

Example 118 Preparation of Compound

Prepared by General Method B (78% yield); ¹H NMR (DMSO-d6, 400 MHz) δ:4.03 (s, 3H), 7.44 (t, J=8.0 Hz, 1H), 7.52 (t, J=8.0 Hz, 2H), 7.64 (d,J=8.0 Hz, 2H), 7.81 (d, J=8.0 Hz, 2H), 7.88 (d, J=8.0 Hz, 2H), 8.09 (m,2H), 8.21-8.24 (m, 1H), 8.54 (d, J=8.0 Hz, 1H), 9.34 (m, 2H).

Example 119 Preparation of Compound

Prepared by General Method A (92% yield); ¹H NMR (CDCl₃, 400 MHz) δ 7.40(m, 2H), 7.48-7.55 (m, 3H), 7.60 (d, J=8.0 Hz, 2H), 7.69 (d, J=8.0 Hz,2H), 7.75 (m, 3H), 8.00 (d, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H), 8.96(d J=4.0 Hz, 1H).

Example 120 Preparation of Compound

Prepared by General Method B (91% yield); ¹H NMR (CDCl₃, 400 MHz) δ:4.99 (s, 3H), 7.37-7.44 (m, 1H), 7.46-7.54 (m, 2H), 7.66-7.70 (m, 4H),7.84-7.86 (m, 2H), 7.9 (t, J=8.0 Hz, 1H), 8.05 (t, J=8.0 Hz, 1H), 8.25(t, J=8.0 Hz, 1H), 8.36 (d, J=8.0 Hz, 1H), 8.51 (m, 1H), 10.31 (m, 1H).

Example 121 Preparation of Compound

Prepared by General Method A from 5-bromoquinoline and4-[1,1′]biphenylboronic acid. ¹H NMR (CDCl₃, 400 MHz) δ: 7.37 (t J=8.0Hz, 1H), 7.49 (t, J=8.0 Hz, 2H), 7.56 (d, J=8.0 Hz, 2H), 7.68-7.76 (m,7H), 8.00 (d, J=8.0 Hz, 1H), 8.51 (d J=8.0 Hz, 1H, 9.32 (s, 1H).

Example 122 Preparation of Compound

Prepared by General Method B; ¹H NMR (DMSO-d6, 400 MHz) δ: 4.76 (s, 3H),7.52 (m, 1H), 7.61 (t, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz, 2H), 7.86 (d,J=8.0 Hz, 2H), 8.00 (d, J=8.0 Hz, 2H), 8.13-8.20 (m, 2H), 8.43 (m, 1H),8.64 (d, J=8.0 Hz, 1H), 9.16 (d, J=8.0 Hz, 1H), 9.60 (d, J=8.0 Hz, 1H).

Comparative Example A

Prepared by General Method B from quinoline (93% yield); ¹H NMR(DMSO-d6, 400 MHz) δ: 4.65 (s, 3H), 8.08 (t, J=8.0 Hz, 1H), 8.19 (m,1H), 8.31 (m, 1H), 8.50 (m, 2H), 9.29 (d, J=8.0 Hz, 1H), 9.51 (d, J=8.0Hz, 1H).

Comparative Example B

Prepared by General Method B from commercially available2-phenylisoquinoline (87% yield); ¹H NMR (DMSO-d6, 400 MHz) δ: 4.40 (s,3H), 7.75 (m, 3H), 7.83 (m, 2H), 8.01 (t, J=8.0 Hz, 1H), 8.18 (d, J=8.0Hz, 1H), 8.35 (m, 1H), 8.54 (d, J=8.0 Hz, 1H), 8.64 (d, J=8.0 Hz, 1H),9.30 (d, J=8.0 Hz, 1H).

Example 123

The following can illustrate representative pharmaceutical dosage forms,containing a compound of formula I (‘Compound X’) or a pharmaceuticallyacceptable salt thereof, for therapeutic or prophylactic use in humans.

(i) Tablet 1 mg/tablet Compound X = 100.0 Lactose 77.5 Povidone 15.0Croscarmellose sodium 12.0 Microcrystalline cellulose 92.5 Magnesiumstearate 3.0 300.0

(ii) Tablet 2 mg/tablet Compound X = 20.0 Microcrystalline cellulose410.0 Starch 50.0 Sodium starch glycolate 15.0 Magnesium stearate 5.0500.0

(iii) Capsule mg/capsule Compound X = 10.0 Colloidal silicon dioxide 1.5Lactose 465.5 Pregelatinized starch 120.0 Magnesium stearate 3.0 600.0

(iv) Injection 1 (1 mg/ml) mg/ml Compound X = (free acid form) 1.0Dibasic sodium phosphate 12.0 Monobasic sodium phosphate 0.7 Sodiumchloride 4.5 1.0 N Sodium hydroxide solution q.s. (pH adjustment to7.0-7.5) Water for injection q.s. ad 1 mL

(v) Injection 2 (10 mg/ml) mg/ml Compound X = (free acid form) 10.0Monobasic sodium phosphate 0.3 Dibasic sodium phosphate 1.1 Polyethyleneglycol 400 200.0 01N Sodium hydroxide solution q.s. (pH adjustment to7.0-7.5) Water for injection q.s. ad 1 mL

(vi) Aerosol mg/can Compound X = 20.0 Oleic acid 10.0Trichloromonofluoromethane 5,000.0 Dichlorodifluoromethane 10,000.0Dichlorotetrafluoroethane 5,000.0The above formulations may be obtained by conventional procedures wellknown in the pharmaceutical art.

All publications, patents, and patent documents are incorporated byreference herein, as though individually incorporated by reference. Theinvention has been described with reference to various specific andpreferred embodiments and techniques. However, it should be understoodthat many variations and modifications may be made while remainingwithin the spirit and scope of the invention.

What is claimed is:
 1. A compound of formula I:

wherein: X is C—R⁵¹; Y is C(R⁵²); R⁵¹ is hydrogen and R⁵² is a ringselected from phenyl, pyridyl, and [D⁻N⁺(C₁-C₆)alkylpyridyl], whereinthe phenyl is substituted with one or more groups selected frommethylenedioxy, R^(5f), R^(5da), and (C₁-C₆)alkyl that is substitutedwith one or more R^(5f), and wherein the pyridyl, and[D⁻N⁺—(C₁-C₆)alkylpyridyl] is optionally substituted with one or moregroups selected from methylenedioxy, Z—R^(5x), R^(5f), R^(5da), and(C₁-C₆)alkyl that is substituted with one or more R^(5f); or R⁵¹ is—N⁺(R^(5a))₃D⁻, —NR^(5g)R^(5h), or (C₁-C₆)alkyl that is substituted withone or more R^(5f); and R⁵² is a ring selected from phenyl, pyridyl, and[D⁻N⁺—(C₁-C₆)alkylpyridyl], which ring is optionally substituted withone or more groups selected from methylenedioxy, Z—R^(5x), R^(5f),R^(5da), and (C₁-C₆)alkyl that is substituted with one or more R^(5f);R⁶ and R⁷ taken together can be methylenedioxy or each R⁶ and R⁷ isindependently selected from H and Z—R^(5x); R⁸ is hydrogen; each Z is—O—; at least one of R⁴ and R⁵ is selected from (C₃-C₆)cycloalkyl, aryl,and heteroaryl; and the remainder of R³, R⁴, and R⁵ are H; wherein eacharyl and heteroaryl of R⁴ and R⁵ is optionally substituted with one ormore groups independently selected from (C₁-C₆)alkyl, halo, and R^(5s);each R^(5a) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl; each R^(5b) isindependently selected from H, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl,(C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl, aryl(C₁-C₆) alkyl andheteroaryl(C₁-C₆)alkyl; each R^(5c) and R^(5d) is independently selectedfrom H, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆) alkyl; whereinany (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl,aryl, heteroaryl, aryl(C₁-C₆) alkyl or heteroaryl(C₁-C₆)alkyl of R^(5c)and R^(5d) is optionally substituted with one or more groupsindependently selected from hydroxy, carboxy, and NR^(5m)R^(5n); eachR^(5e) is independently selected from H, (C₁-C₆)alkyl,(C₃-C₆)cycloalkyl, (C₃-C₆)cycloalkyl(C₁-C₆)alkyl, aryl, heteroaryl,aryl(C₁-C₆) alkyl and heteroaryl(C₁-C₆)alkyl; each R^(5f) isindependently selected from —N⁺(R^(5a))₃D⁻, —C(═NR^(5b))—NR^(5c)R^(5d),—NR^(5e)—C(═NR^(5b))—NR^(5c)R^(5d), and —NR^(5g)R^(5h); each R^(5g) andR^(5h) is independently selected from H, and (C₁-C₆)alkyl; wherein any(C₁-C₆)alkyl of R^(5g) and R^(5h) is optionally substituted with one ormore groups independently selected from hydroxy, carboxy, andNR^(5m)R^(5n); each R^(5m) and R^(5n) is independently selected from H,and (C₁-C₆)alkyl; each R^(5s) is independently trifluoromethyl,trifluoromethoxy, aryl, or heteroaryl, wherein each aryl and heteroarylis optionally substituted with one or more (C₁-C₆)alkyl, halo, hydroxy,cyano, nitro, (C₁-C₆)alkoxy, (C₃-C₆)cycloalkyl, carboxy,trifluoromethyl, and trifluoromethoxy; each R^(5x) is independentlyselected from (C₁-C₆)alkyl; each D⁻ is independently a counter anion;each R^(5da) is carboxy or (C₁-C₆)alkoxycarbonyl; and the bondrepresented by ---- is present; or a salt or prodrug thereof.
 2. Thecompound

or a salt thereof.
 3. A compound selected from the group consisting of

wherein R^(54′) and R^(5′) are each H or methoxy, or taken together aremethylenedioxy and B is an acceptable counterion; or a salt or prodrugthereof.
 4. A compound selected from the group consisting of

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy and B is an acceptable counterion; or a salt or prodrugthereof.
 5. A compound selected from the group consisting of

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy and A is an acceptable counterion; or a salt or prodrugthereof.
 6. A compound selected from the group consisting of

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy; or a salt or prodrug thereof.
 7. A compound selectedfrom the group consisting of

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy; or a salt or prodrug thereof.
 8. A compound selectedfrom the group consisting of

wherein R^(54′) and R^(55′) are each H or methoxy, or taken together aremethylenedioxy; or a salt or prodrug thereof.
 9. A compound selectedfrom the group consisting of

or a salt or prodrug thereof.
 10. A compound selected from the groupconsisting of

or a salt or prodrug thereof.
 11. A compound selected from the groupconsisting of

or a prodrug thereof wherein each compound is independently associatedwith a counterion.
 12. The compound:

or a salt or prodrug thereof.
 13. A composition comprising a compound offormula I as described in claim 1 or a pharmaceutically acceptable saltor prodrug thereof, and a pharmaceutically acceptable vehicle.